Is PC p.Ala307Val (c.920C>T) pathogenic?

PC p.Ala307Val (c.920C>T) is classified Uncertain significance in PC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-09-16). AlphaMissense: ambiguous (0.5034); Very rare (popmax 0.00534%, afr).

How common is PC p.Ala307Val (c.920C>T) in the general population?

PC p.Ala307Val (c.920C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about PC p.Ala307Val (c.920C>T)?

AlphaMissense predicts ambiguous (score 0.5034) — an in-silico prediction, not a clinical call.

PC p.Ala307Val

c.920C>T · rs1247838963 · VCV591223

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5034 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5034	ambiguous
REVEL	0.935	strongly pathogenic-leaning
SaProt	LLR -7.35	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.93, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 23 kb · p 3.1e-25 · regional, not allelic
Overall
CADD	29.7	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 0.00534% African / African-American · 4/74,938 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,613,698 alleles · very rare exomes 2/1,461,494 · genomes 2/152,204 · joint denominator

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: PC
Protein: p.Ala307Val
Coding: c.920C>T
MANE Select: NM_001040716
dbSNP: rs1247838963
Type: single nucleotide variant
Location: chr11:66868948 (GRCh38)
Gene constraint: LOEUF 0.539 · pLI 0.07 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.53 · 10 PDB
Residue 307: the biotin carboxylation domain; the atp-grasp domain; a β-strand

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

Similar variants

PC p.Ala307Thr Uncertain significance ★ ⚠ same residue
PC p.Ala307= Likely benign ★ same residue
PC c.1368+1G>A Likely pathogenic ★★ same type
PC c.1826-1G>C Likely pathogenic ★★ same type
PC c.1983-116C>T Likely pathogenic ★★ same type
PC c.633+2T>C Likely pathogenic ★★ same type
PC p.Ala610Thr Pathogenic ★★ same type
PC p.Ala812Asp Likely pathogenic ★★ 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/pc-p-ala307val (accessed [today's date]).

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