Is INTS11 p.Val380Ile (c.1138G>A) pathogenic?

INTS11 p.Val380Ile (c.1138G>A) is classified Uncertain significance in INTS11 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely benign (0.0999); Rare (popmax 0.132%, mid).

How common is INTS11 p.Val380Ile (c.1138G>A) in the general population?

INTS11 p.Val380Ile (c.1138G>A) is rare (popmax 0.132%, mid) (gnomAD).

What do computational predictors say about INTS11 p.Val380Ile (c.1138G>A)?

AlphaMissense predicts likely benign (score 0.0999) — an in-silico prediction, not a clinical call.

INTS11 p.Val380Ile

c.1138G>A · rs143110978 · VCV3110082

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0999 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.132%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0999	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -9.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.9	GERP 2.3, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.087 · regional, not allelic
Overall
CADD	21.5	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

Grpmax group 0.132% Middle Eastern · 8/6,058 alleles

Filtering AF 0.0657% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.048%

Overall 0.0163% 262/1,611,806 alleles · rare exomes 223/1,459,400 · genomes 39/152,406 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.132%	757
African / African-American	0.0453%	2,208
Remaining individualsnot grpmax-eligible	0.0192%	5,204
Admixed American	0.0183%	5,456
European (non-Finnish)	0.0156%	6,409
Finnishnot grpmax-eligible	0.0112%	8,945
East Asian	0.0111%	8,972
South Asian	0.0011%	91,062

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.Val380Ile
Coding: c.1138G>A
MANE Select: NM_017871
dbSNP: rs143110978
Type: single nucleotide variant
Location: chr1:1312943 (GRCh38)
Gene constraint: LOEUF 1.223 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 15 PDB
Residue 380: 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-val380ile (accessed [today's date]).

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