Is INTS1 p.Ala367Val (c.1100C>T) pathogenic?

INTS1 p.Ala367Val (c.1100C>T) is classified Uncertain significance in INTS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-20). AlphaMissense: likely benign (0.1483); Ultra-rare (popmax 0.0124%, amr).

How common is INTS1 p.Ala367Val (c.1100C>T) in the general population?

INTS1 p.Ala367Val (c.1100C>T) is ultra-rare (popmax 0.0124%, amr) (gnomAD).

What do computational predictors say about INTS1 p.Ala367Val (c.1100C>T)?

AlphaMissense predicts likely benign (score 0.1483) — an in-silico prediction, not a clinical call.

INTS1 p.Ala367Val

c.1100C>T · rs757464215 · VCV2506677

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1483 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0124%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1483	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -2.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 21 kb · p 0.12 · regional, not allelic
Overall
CADD	23.0	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 0.0124% Admixed American · 5/40,232 alleles

Filtering AF 0.00485% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00313%

Overall 0.0015% 20/1,334,976 alleles · ultra-rare exomes 19/1,209,624 · genomes 1/125,352 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0124%	8,046
East Asian	0.0048%	20,830
Remaining individualsnot grpmax-eligible	0.00427%	23,441
South Asian	0.00366%	27,297
European (non-Finnish)	0.000882%	113,324

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: INTS1
Protein: p.Ala367Val
Coding: c.1100C>T
MANE Select: NM_001080453
dbSNP: rs757464215
Type: single nucleotide variant
Location: chr7:1499012 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.49 · 8 PDB
Residue 367: an α-helix

Full INTS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

INTS1 c.3430-2A>C Likely pathogenic ★★ same type
INTS1 p.Arg101Ter Likely pathogenic ★★ same type
INTS1 p.Glu182Ter Likely pathogenic ★★ same type
INTS1 c.1283+5G>A Uncertain significance ★★ same type
INTS1 c.2977-5C>T Uncertain significance ★★ same type
INTS1 p.Ala1112Val Uncertain significance ★★ ⚠ same type
INTS1 p.Ala1505Val Uncertain significance ★★ ⚠ same type
INTS1 p.Ala1854Val Uncertain significance ★★ ⚠ 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/ints1-p-ala367val (accessed [today's date]).

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