Is ATPAF2 p.Pro147= (c.441C>T) pathogenic?

ATPAF2 p.Pro147= (c.441C>T) is classified Likely benign in ATPAF2 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-08-29). Ultra-rare (popmax 0.0208%, nfe).

How common is ATPAF2 p.Pro147= (c.441C>T) in the general population?

ATPAF2 p.Pro147= (c.441C>T) is ultra-rare (popmax 0.0208%, nfe) (gnomAD).

ATPAF2 p.Pro147=

c.441C>T · rs138666486 · VCV2901817

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0208%, nfe)

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 -0.29	GERP -2, phastCons 0.41
Overall
CADD	7.283	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0208% European (non-Finnish) · 245/1,179,708 alleles

Filtering AF 0.0186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.0157% 253/1,613,670 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0208%	4,815
Remaining individualsnot grpmax-eligible	0.0064%	15,625
South Asian	0.00329%	30,357
East Asian	0.00223%	44,890

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.Pro147=
Coding: c.441C>T
MANE Select: NM_145691
dbSNP: rs138666486
Type: single nucleotide variant
Location: chr17:18024686 (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-pro147 (accessed [today's date]).

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