Is ATRIP p.Glu62Asp (c.186G>C) pathogenic?

ATRIP p.Glu62Asp (c.186G>C) is classified Uncertain significance in ATRIP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-21). AlphaMissense: likely pathogenic (0.5893); Ultra-rare (popmax 0.0254%, eas).

How common is ATRIP p.Glu62Asp (c.186G>C) in the general population?

ATRIP p.Glu62Asp (c.186G>C) is ultra-rare (popmax 0.0254%, eas) (gnomAD).

What do computational predictors say about ATRIP p.Glu62Asp (c.186G>C)?

AlphaMissense predicts likely pathogenic (score 0.5893) — an in-silico prediction, not a clinical call.

ATRIP p.Glu62Asp

c.186G>C · VCV3464139

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5893 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5893	likely pathogenic
REVEL	0.116	moderately benign-leaning
SaProt	LLR -7.68	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -0.99, phastCons 0.57
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.089 · regional, not allelic
Overall
CADD	22.1	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 0.0254% East Asian · 10/39,302 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0104%

Overall 0.000704% 10/1,419,658 alleles · ultra-rare

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.Glu62Asp
Coding: c.186G>C
MANE Select: NM_130384
Type: single nucleotide variant
Location: chr3:48447031 (GRCh38)
Gene constraint: LOEUF 0.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.10 · 24 PDB
Residue 62: an α-helix

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

Similar variants

TREX1 p.Arg62Cys Uncertain significance ★★ ⚠ same residue
TREX1 p.Arg62His Uncertain significance ★★ ⚠ same residue
TREX1 p.Arg62Leu Uncertain significance ★ same residue
ATRIP p.Glu62= 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

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-glu62asp (accessed [today's date]).

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