Is ATRIP p.Leu174= (c.522C>G) pathogenic?

ATRIP p.Leu174= (c.522C>G) is classified Likely benign in ATRIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-24). Very rare (popmax 0.00337%, amr).

How common is ATRIP p.Leu174= (c.522C>G) in the general population?

ATRIP p.Leu174= (c.522C>G) is very rare (popmax 0.00337%, amr) (gnomAD).

ATRIP p.Leu174=

c.522C>G · rs141432992 · VCV2959269

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00337%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.066	GERP -3, phastCons 0.6
Overall
CADD	7.663	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00337% Admixed American · 2/59,270 alleles

Filtering AF 0.00248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00218%

Overall 0.00274% 44/1,608,298 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00337%	29,635
European (non-Finnish)	0.00331%	30,181
Remaining individualsnot grpmax-eligible	0.00321%	31,148
African / African-American	0.00134%	74,742

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.Leu174=
Coding: c.522C>G
MANE Select: NM_130384
dbSNP: rs141432992
Type: single nucleotide variant
Location: chr3:48451869 (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.Leu174His Uncertain significance ★ ⚠ same residue
ATRIP p.Leu174Phe Uncertain significance ★ ⚠ same residue
TREX1 p.Arg174Gly Uncertain significance ★ ⚠ same residue
TREX1 p.Arg174Lys Uncertain significance ★ ⚠ same residue
TREX1 p.Arg174_Lys175delinsSerTer Pathogenic ★ 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-leu174 (accessed [today's date]).

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