Is ATPAF2 p.Val81Ile (c.241G>A) pathogenic?

ATPAF2 p.Val81Ile (c.241G>A) is classified Conflicting classifications of pathogenicity in ATPAF2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-04-30). AlphaMissense: likely benign (0.1451); Rare (popmax 0.232%, sas).

How common is ATPAF2 p.Val81Ile (c.241G>A) in the general population?

ATPAF2 p.Val81Ile (c.241G>A) is rare (popmax 0.232%, sas) (gnomAD).

What do computational predictors say about ATPAF2 p.Val81Ile (c.241G>A)?

AlphaMissense predicts likely benign (score 0.1451) — an in-silico prediction, not a clinical call.

ATPAF2 p.Val81Ile

c.241G>A · rs371136012 · VCV498915

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1451 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.232%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1451	likely benign
REVEL	0.318	indeterminate
SaProt	LLR -10.37	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.58, phastCons 0.99
Regional constraint	o/e 0.58	unconstrained · MANE · 12 kb · p 5.5e-05 · regional, not allelic
Overall
CADD	20.4	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 0.232% South Asian · 211/91,074 alleles

Filtering AF 0.206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.196%

Overall 0.0147% 238/1,614,124 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.232%	432
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)	0.00186%	53,637
Admixed American	0.00167%	60,026
African / African-American	0.00133%	75,034

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: ATPAF2
Protein: p.Val81Ile
Coding: c.241G>A
MANE Select: NM_145691
dbSNP: rs371136012
Type: single nucleotide variant
Location: chr17:18028315 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.07

Full ATPAF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATPAF2 c.-90C>A Uncertain significance ★★ same type
ATPAF2 c.*132C>T Uncertain significance ★★ same type
ATPAF2 p.Ala130Glu Uncertain significance ★★ ⚠ same type
ATPAF2 p.Ala267Thr Uncertain significance ★★ ⚠ same type
ATPAF2 p.Ala268Thr Uncertain significance ★★ ⚠ same type
ATPAF2 p.Arg14Gly Uncertain significance ★★ ⚠ same type
ATPAF2 p.Arg189Gln Uncertain significance ★★ ⚠ same type
ATPAF2 p.Arg189Trp 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/atpaf2-p-val81ile (accessed [today's date]).

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