Is ATRIP p.Asp46His (c.136G>C) pathogenic?

ATRIP p.Asp46His (c.136G>C) is classified Uncertain significance in ATRIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-02). AlphaMissense: likely benign (0.1553); Absent from gnomAD v4.1.

How common is ATRIP p.Asp46His (c.136G>C) in the general population?

ATRIP p.Asp46His (c.136G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATRIP p.Asp46His (c.136G>C)?

AlphaMissense predicts likely benign (score 0.1553) — an in-silico prediction, not a clinical call.

ATRIP p.Asp46His

c.136G>C · VCV3811225

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1553 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1553	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -8.46	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 9.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.089 · regional, not allelic
Overall
CADD	25.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ATRIP
Protein: p.Asp46His
Coding: c.136G>C
MANE Select: NM_130384
Type: single nucleotide variant
Location: chr3:48446981 (GRCh38)
Gene constraint: LOEUF 0.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.10 · 24 PDB
Residue 46: the 'disordered' region

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

Similar variants

TREX1 p.Ser46Thr Uncertain significance ★ ⚠ same residue
ATRIP p.Asp46Glu Likely benign ★ same residue
TREX1 p.Ser46= Likely benign ★ same residue
TREX1 p.Ser46fs Pathogenic/Likely pathogenic ★ same residue
ATRIP p.Asp46_Asp47insProAsp Uncertain significance ★ same residue
TREX1 p.Arg114His Pathogenic/Likely pathogenic ★★ ⚠ same type
TREX1 p.Arg164Ter Pathogenic/Likely pathogenic ★★ same type
TREX1 p.Asp18Asn 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-asp46his (accessed [today's date]).

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