Is ATPAF2 p.Ser54Ile (c.161G>T) pathogenic?

ATPAF2 p.Ser54Ile (c.161G>T) is classified Uncertain significance in ATPAF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-25). AlphaMissense: ambiguous (0.5206); Absent from gnomAD v4.1.

How common is ATPAF2 p.Ser54Ile (c.161G>T) in the general population?

ATPAF2 p.Ser54Ile (c.161G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATPAF2 p.Ser54Ile (c.161G>T)?

AlphaMissense predicts ambiguous (score 0.5206) — an in-silico prediction, not a clinical call.

ATPAF2 p.Ser54Ile

c.161G>T · VCV4686749

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5206 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5206	ambiguous
REVEL	0.68	pathogenic-leaning
SaProt	LLR -10.67	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.88	GERP 0.83, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 12 kb · p 5.5e-05 · regional, not allelic
Overall
CADD	24.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ATPAF2
Protein: p.Ser54Ile
Coding: c.161G>T
MANE Select: NM_145691
Type: single nucleotide variant
Location: chr17:18028632 (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 p.Ser54Thr Uncertain significance ★ ⚠ same residue
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

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-ser54ile (accessed [today's date]).

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