Is ATP5MC2 p.Pro11Ser (c.31C>T) pathogenic?

ATP5MC2 p.Pro11Ser (c.31C>T) is classified Uncertain significance in ATP5MC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely benign (0.0802); Very rare (popmax 0.00186%, amr).

How common is ATP5MC2 p.Pro11Ser (c.31C>T) in the general population?

ATP5MC2 p.Pro11Ser (c.31C>T) is very rare (popmax 0.00186%, amr) (gnomAD).

What do computational predictors say about ATP5MC2 p.Pro11Ser (c.31C>T)?

AlphaMissense predicts likely benign (score 0.0802) — an in-silico prediction, not a clinical call.

ATP5MC2 p.Pro11Ser

c.31C>T · VCV4644333

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0802 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0802	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -4.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -0.18, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 7,297 bp · p 0.0012 · regional, not allelic
Overall
CADD	14.66	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 0.00186% Admixed American · 1/53,844 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000253% 4/1,579,742 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00186%	53,844
European (non-Finnish)	0.000258%	387,511

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: ATP5MC2
Protein: p.Pro11Ser
Coding: c.31C>T
MANE Select: NM_005176
Type: single nucleotide variant
Location: chr12:53672584 (GRCh38)
Gene constraint: LOEUF 1.471 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.83

Full ATP5MC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATP5MC2 c.-14C>T Uncertain significance ★ same type
ATP5MC2 c.-42A>G Uncertain significance ★ same type
ATP5MC2 c.-51C>G Uncertain significance ★ same type
ATP5MC2 c.-60C>T Uncertain significance ★ same type
ATP5MC2 c.-9C>T Uncertain significance ★ same type
ATP5MC2 p.Arg23His Uncertain significance ★ ⚠ same type
ATP5MC2 p.Arg34Gly Uncertain significance ★ same type
ATP5MC2 p.Asp69Asn 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/atp5mc2-p-pro11ser (accessed [today's date]).

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