Is ATRIP p.His52Arg (c.155A>G) pathogenic?

ATRIP p.His52Arg (c.155A>G) is classified Uncertain significance in ATRIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-04). AlphaMissense: likely benign (0.099); Very rare (popmax 0.0014%, afr).

How common is ATRIP p.His52Arg (c.155A>G) in the general population?

ATRIP p.His52Arg (c.155A>G) is very rare (popmax 0.0014%, afr) (gnomAD).

What do computational predictors say about ATRIP p.His52Arg (c.155A>G)?

AlphaMissense predicts likely benign (score 0.099) — an in-silico prediction, not a clinical call.

ATRIP p.His52Arg

c.155A>G · rs2039693370 · VCV2866249

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.099 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0014%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.099	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -5.72	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 6.7	GERP 0.73, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.089 · regional, not allelic
Overall
CADD	21.4	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 0.0014% African / African-American · 1/71,570 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00028% 4/1,427,498 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0014%	71,570
European (non-Finnish)	0.000257%	388,665

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.His52Arg
Coding: c.155A>G
MANE Select: NM_130384
dbSNP: rs2039693370
Type: single nucleotide variant
Location: chr3:48447000 (GRCh38)
Gene constraint: LOEUF 0.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.10 · 24 PDB
Residue 52: the 'disordered' region

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

Similar variants

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
ATRIP p.Ala374Thr 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-his52arg (accessed [today's date]).

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