Is ATRIP p.Glu113Lys (c.337G>A) pathogenic?

ATRIP p.Glu113Lys (c.337G>A) is classified Uncertain significance in ATRIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-19). AlphaMissense: likely benign (0.2704); Ultra-rare (popmax 0.0103%, nfe).

How common is ATRIP p.Glu113Lys (c.337G>A) in the general population?

ATRIP p.Glu113Lys (c.337G>A) is ultra-rare (popmax 0.0103%, nfe) (gnomAD).

What do computational predictors say about ATRIP p.Glu113Lys (c.337G>A)?

AlphaMissense predicts likely benign (score 0.2704) — an in-silico prediction, not a clinical call.

ATRIP p.Glu113Lys

c.337G>A · rs149518027 · VCV1431006

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2704 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2704	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	LLR -6.93	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 8.3	GERP 0.73, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.089 · regional, not allelic
Overall
CADD	23.8	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 0.0103% European (non-Finnish) · 122/1,179,630 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00828%

Overall 0.00812% 131/1,612,826 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0103%	9,669
African / African-American	0.00534%	18,720
Remaining individualsnot grpmax-eligible	0.0032%	31,230
South Asian	0.00221%	45,294
Admixed American	0.00167%	59,854

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.Glu113Lys
Coding: c.337G>A
MANE Select: NM_130384
dbSNP: rs149518027
Type: single nucleotide variant
Location: chr3:48450126 (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

TREX1 p.Arg113= Likely benign ★★ same residue
ATRIP p.Glu113Ter Uncertain significance ★ same residue
ATRIP p.Glu113Val Uncertain significance ★ ⚠ same residue
TREX1 p.Arg113Gln Uncertain significance ★ ⚠ same residue
TREX1 p.Arg113Gly Uncertain significance ★ ⚠ same residue
TREX1 p.Arg113Leu Uncertain significance ★ ⚠ 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-glu113lys (accessed [today's date]).

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