Is ATRIP p.Asp46Glu (c.138C>G) pathogenic?

ATRIP p.Asp46Glu (c.138C>G) is classified Likely benign in ATRIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: likely benign (0.0658); Very rare (popmax 0.00703%, afr).

How common is ATRIP p.Asp46Glu (c.138C>G) in the general population?

ATRIP p.Asp46Glu (c.138C>G) is very rare (popmax 0.00703%, afr) (gnomAD).

What do computational predictors say about ATRIP p.Asp46Glu (c.138C>G)?

AlphaMissense predicts likely benign (score 0.0658) — an in-silico prediction, not a clinical call.

ATRIP p.Asp46Glu

c.138C>G · VCV4644573

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0658 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00703%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0658	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -6.13	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 0.18	GERP -2.9, phastCons 0.26
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.089 · regional, not allelic
Overall
CADD	2.336	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 0.00703% African / African-American · 5/71,162 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00179%

Overall 0.000445% 7/1,573,726 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00703%	14,232
Remaining individualsnot grpmax-eligible	0.00165%	60,746
European (non-Finnish)	8.6e-05%	1,163,398

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.Asp46Glu
Coding: c.138C>G
MANE Select: NM_130384
Type: single nucleotide variant
Location: chr3:48446983 (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

ATRIP p.Asp46His Uncertain significance ★ ⚠ same residue
TREX1 p.Ser46Thr Uncertain significance ★ ⚠ 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-asp46glu (accessed [today's date]).

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