Is ATRIP p.His261Asp (c.781C>G) pathogenic?

ATRIP p.His261Asp (c.781C>G) is classified Likely benign in ATRIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-06). AlphaMissense: likely benign (0.1365); Very rare (popmax 0.00689%, amr).

How common is ATRIP p.His261Asp (c.781C>G) in the general population?

ATRIP p.His261Asp (c.781C>G) is very rare (popmax 0.00689%, amr) (gnomAD).

What do computational predictors say about ATRIP p.His261Asp (c.781C>G)?

AlphaMissense predicts likely benign (score 0.1365) — an in-silico prediction, not a clinical call.

ATRIP p.His261Asp

c.781C>G · VCV3810209

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1365 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00689%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1365	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -5.75	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 0.62	GERP -1.9, phastCons 0.002
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.089 · regional, not allelic
Overall
CADD	14.08	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 0.00689% Admixed American · 4/58,034 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00138%

Overall 0.00025% 4/1,600,330 alleles · very 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.His261Asp
Coding: c.781C>G
MANE Select: NM_130384
Type: single nucleotide variant
Location: chr3:48457368 (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.His261Gln Uncertain significance ★★ ⚠ same residue
TREX1 p.Ser261= Likely benign ★★ same residue
ATRIP p.His261Tyr Uncertain significance ★ ⚠ same residue
TREX1 p.Ser261Gly Uncertain significance ★ ⚠ same residue
TREX1 p.Ser261Thr Uncertain significance ★ ⚠ same residue
ATRIP p.His261Pro Likely benign ★ same residue
TREX1 p.Arg114His Pathogenic/Likely pathogenic ★★ ⚠ same type
TREX1 p.Arg164Ter Pathogenic/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-his261asp (accessed [today's date]).

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