Is INTS11 p.Gly55Ser (c.163G>A) pathogenic?

INTS11 p.Gly55Ser (c.163G>A) is classified Uncertain significance in INTS11 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-07-02). AlphaMissense: likely benign (0.1891); Very rare (popmax 0.0011%, sas); Associated with neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities.

How common is INTS11 p.Gly55Ser (c.163G>A) in the general population?

INTS11 p.Gly55Ser (c.163G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about INTS11 p.Gly55Ser (c.163G>A)?

AlphaMissense predicts likely benign (score 0.1891) — an in-silico prediction, not a clinical call.

INTS11 p.Gly55Ser

Q: What condition is associated with INTS11 p.Gly55Ser (c.163G>A)?

INTS11 p.Gly55Ser (c.163G>A) is associated with neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities (ClinVar).

c.163G>A · rs779574336 · VCV2506982

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1891 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities

Computational evidence

Protein change
AlphaMissense	0.1891	likely benign
REVEL	0.703	pathogenic-leaning
SaProt	LLR -7.18	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.087 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,078 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000682% 11/1,613,826 alleles · very rare exomes 7/1,461,632 · genomes 4/152,194 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,474
South Asiangrpmax	0.0011%	91,078
European (non-Finnish)	0.000763%	131,109

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: INTS11
Protein: p.Gly55Ser
Coding: c.163G>A
MANE Select: NM_017871
dbSNP: rs779574336
Type: single nucleotide variant
Location: chr1:1320493 (GRCh38)
Gene constraint: LOEUF 1.223 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 15 PDB
Residue 55: a UniProt-annotated variant site (in nedmlob; uncertain significance; may affect function; the orthologous mutation in ints11-deficient drosophila is unable to rescue locomotor defects); a β-strand

Full INTS11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

INTS11 c.28+1406C>T Uncertain significance ★★ same condition
INTS11 p.Arg231Cys Uncertain significance ★★ ⚠ same condition
INTS11 p.Glu227Lys Uncertain significance ★★ same condition
INTS11 c.1738-1G>A Likely pathogenic ★ same condition
INTS11 p.Arg17Leu Pathogenic ★ same condition
INTS11 p.Arg43Ter Pathogenic ★ same condition
INTS11 p.Glu554Gly Uncertain significance ★ ⚠ same condition
INTS11 p.Gly455Ser Uncertain significance ★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ints11-p-gly55ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown