Is ATRIP p.Val493Ile (c.1477G>A) pathogenic?

ATRIP p.Val493Ile (c.1477G>A) is classified Uncertain significance in ATRIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-17). AlphaMissense: likely benign (0.1087); Rare (popmax 0.182%, mid).

How common is ATRIP p.Val493Ile (c.1477G>A) in the general population?

ATRIP p.Val493Ile (c.1477G>A) is rare (popmax 0.182%, mid) (gnomAD).

What do computational predictors say about ATRIP p.Val493Ile (c.1477G>A)?

AlphaMissense predicts likely benign (score 0.1087) — an in-silico prediction, not a clinical call.

ATRIP p.Val493Ile

c.1477G>A · rs199783860 · VCV2725063

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1087 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.182%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1087	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -8.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.72, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.089 · regional, not allelic
Overall
CADD	19.7	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 0.182% Middle Eastern · 11/6,060 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0787%

Overall 0.00291% 47/1,614,028 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.182%	551
Remaining individualsnot grpmax-eligible	0.0112%	8,929
East Asian	0.00446%	22,444
European (non-Finnish)	0.00195%	51,304
Admixed American	0.00167%	59,990
Finnishnot grpmax-eligible	0.00156%	64,024
African / African-American	0.00133%	75,036
South Asian	0.0011%	91,032

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: ATRIP
Protein: p.Val493Ile
Coding: c.1477G>A
MANE Select: NM_130384
dbSNP: rs199783860
Type: single nucleotide variant
Location: chr3:48460531 (GRCh38)
Gene constraint: LOEUF 0.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.10 · 24 PDB

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

Similar variants

ATRIP p.Val493= Likely benign ★ same residue
TREX1 p.Arg114His Pathogenic/Likely pathogenic ★★ ⚠ same type
TREX1 p.Arg164Ter Pathogenic/Likely pathogenic ★★ same type
TREX1 p.Asp18Asn Pathogenic ★★ same type
TREX1 p.Asp200His Likely pathogenic ★★ same type
TREX1 p.Gln135Ter Pathogenic/Likely pathogenic ★★ same type
ATRIP p.Ala119Thr Uncertain significance ★★ ⚠ same type
ATRIP p.Ala173Val 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/atrip-p-val493ile (accessed [today's date]).

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