Is ATRIP p.Ser334Arg (c.1000A>C) pathogenic?

ATRIP p.Ser334Arg (c.1000A>C) is classified Uncertain significance in ATRIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-06-06). AlphaMissense: likely pathogenic (0.6763); Very rare (popmax 0.0011%, nfe).

How common is ATRIP p.Ser334Arg (c.1000A>C) in the general population?

ATRIP p.Ser334Arg (c.1000A>C) is very rare (popmax 0.0011%, nfe) (gnomAD).

What do computational predictors say about ATRIP p.Ser334Arg (c.1000A>C)?

AlphaMissense predicts likely pathogenic (score 0.6763) — an in-silico prediction, not a clinical call.

ATRIP p.Ser334Arg

c.1000A>C · rs1660968456 · VCV2094590

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6763 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6763	likely pathogenic
REVEL	0.226	benign-leaning
SaProt	LLR -7.27	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 9.3	GERP 1.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.089 · regional, not allelic
Overall
CADD	22.7	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 0.0011% European (non-Finnish) · 13/1,179,932 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000889% 13/1,461,754 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.Ser334Arg
Coding: c.1000A>C
MANE Select: NM_130384
dbSNP: rs1660968456
Type: single nucleotide variant
Location: chr3:48459861 (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.Ser334Asn Uncertain significance ★ ⚠ same residue
ATRIP p.Ser334= 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

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-ser334arg (accessed [today's date]).

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