Is ATRAID p.Leu9Phe (c.25C>T) pathogenic?

ATRAID p.Leu9Phe (c.25C>T) is classified Uncertain significance in ATRAID (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.0602); Ultra-rare (popmax 0.0178%, afr).

How common is ATRAID p.Leu9Phe (c.25C>T) in the general population?

ATRAID p.Leu9Phe (c.25C>T) is ultra-rare (popmax 0.0178%, afr) (gnomAD).

What do computational predictors say about ATRAID p.Leu9Phe (c.25C>T)?

AlphaMissense predicts likely benign (score 0.0602) — an in-silico prediction, not a clinical call.

ATRAID p.Leu9Phe

c.25C>T · rs185160026 · VCV3132107

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0602 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0602	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -8.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.22	donor gain · deltas
Constraint at this position
Conservation	phyloP -3.7	GERP -4.7
Regional constraint	o/e 1.08	unconstrained · MANE · 4,576 bp · p 0.19 · regional, not allelic
Overall
CADD	1.307	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 0.0178% African / African-American · 13/73,096 alleles

Filtering AF 0.0105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00831%

Overall 0.00103% 16/1,551,070 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0178%	5,623
European (non-Finnish)	0.000262%	382,409

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: ATRAID
Protein: p.Leu9Phe
Coding: c.25C>T
MANE Select: NM_001170795
dbSNP: rs185160026
Type: single nucleotide variant
Location: chr2:27212393 (GRCh38)
Gene constraint: LOEUF 1.235 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.31

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

Similar variants

ATRAID c.-117C>A Uncertain significance ★ same type
ATRAID c.-123A>C Uncertain significance ★ same type
ATRAID c.-155G>A Uncertain significance ★ same type
ATRAID c.-161A>G Uncertain significance ★ same type
ATRAID c.-24A>T Uncertain significance ★ same type
ATRAID c.-38C>T Uncertain significance ★ same type
ATRAID c.-44C>G Uncertain significance ★ same type
ATRAID c.-71G>A 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/atraid-p-leu9phe (accessed [today's date]).

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