Is INTS11 p.Glu554Gly (c.1661A>G) pathogenic?

INTS11 p.Glu554Gly (c.1661A>G) is classified Uncertain significance in INTS11 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-26). AlphaMissense: likely benign (0.2122); No allele count reported in gnomAD v4.1 (AN 1,576,206); Associated with neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities.

How common is INTS11 p.Glu554Gly (c.1661A>G) in the general population?

INTS11 p.Glu554Gly (c.1661A>G) is no allele count reported in gnomAD v4.1 (AN 1,576,206) (gnomAD).

What do computational predictors say about INTS11 p.Glu554Gly (c.1661A>G)?

AlphaMissense predicts likely benign (score 0.2122) — an in-silico prediction, not a clinical call.

INTS11 p.Glu554Gly

Q: What condition is associated with INTS11 p.Glu554Gly (c.1661A>G)?

INTS11 p.Glu554Gly (c.1661A>G) is associated with neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities (ClinVar).

c.1661A>G · VCV4855074

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2122 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,576,206)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.2122	likely benign
REVEL	0.328	indeterminate
SaProt	LLR -3.75	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.33	acceptor gain · deltas
Pangolin	Δ0.47	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.087 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,576,206). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: INTS11
Protein: p.Glu554Gly
Coding: c.1661A>G
MANE Select: NM_017871
Type: single nucleotide variant
Location: chr1:1312094 (GRCh38)
Gene constraint: LOEUF 1.223 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 15 PDB

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.Gly455Ser Uncertain significance ★ ⚠ same condition
INTS11 p.Gly55Ser 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-glu554gly (accessed [today's date]).

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