Is INTS11 p.Gly26Ser (c.76G>A) pathogenic?

INTS11 p.Gly26Ser (c.76G>A) is classified Uncertain significance in INTS11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely benign (0.1771); Very rare (popmax 0.000339%, nfe).

How common is INTS11 p.Gly26Ser (c.76G>A) in the general population?

INTS11 p.Gly26Ser (c.76G>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about INTS11 p.Gly26Ser (c.76G>A)?

AlphaMissense predicts likely benign (score 0.1771) — an in-silico prediction, not a clinical call.

INTS11 p.Gly26Ser

c.76G>A · VCV4275913

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1771 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1771	likely benign
REVEL	0.651	pathogenic-leaning
SaProt	LLR -10.20	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does 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 1.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.087 · regional, not allelic
Overall
CADD	25.3	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 0.000339% European (non-Finnish) · 4/1,179,888 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,612,964 alleles · very rare exomes 3/1,460,740 · genomes 1/152,224 · joint denominator

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.Gly26Ser
Coding: c.76G>A
MANE Select: NM_017871
Type: single nucleotide variant
Location: chr1:1321046 (GRCh38)
Gene constraint: LOEUF 1.223 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 15 PDB
Residue 26: a β-strand

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

Similar variants

INTS11 c.28+1406C>T Uncertain significance ★★ same type
INTS11 p.Ala241Thr Uncertain significance ★★ ⚠ same type
INTS11 p.Arg231Cys Uncertain significance ★★ ⚠ same type
INTS11 p.Gln467His Uncertain significance ★★ ⚠ same type
INTS11 p.Glu227Lys Uncertain significance ★★ same type
INTS11 p.His157Arg Uncertain significance ★★ ⚠ same type
INTS11 c.1607+18C>A Benign ★★ same type
INTS11 p.Arg196= Benign ★★ same type

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-gly26ser (accessed [today's date]).

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