Is PC p.Val310Met (c.928G>A) pathogenic?

PC p.Val310Met (c.928G>A) is classified Uncertain significance in PC (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-12). AlphaMissense: likely pathogenic (0.6149); Ultra-rare (popmax 0.0112%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PC p.Val310Met (c.928G>A)?

PC p.Val310Met (c.928G>A) is associated with Inborn genetic diseases (ClinVar).

How common is PC p.Val310Met (c.928G>A) in the general population?

PC p.Val310Met (c.928G>A) is ultra-rare (popmax 0.0112%, nfe) (gnomAD).

What do computational predictors say about PC p.Val310Met (c.928G>A)?

AlphaMissense predicts likely pathogenic (score 0.6149) — an in-silico prediction, not a clinical call.

PC p.Val310Met

c.928G>A · rs145970773 · VCV2403964

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6149 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6149	likely pathogenic
REVEL	0.87	moderately pathogenic-leaning
SaProt	LLR -10.40	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 23 kb · p 3.1e-25 · regional, not allelic
Overall
CADD	28.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0112% European (non-Finnish) · 132/1,179,846 alleles

Filtering AF 0.00961% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00904%

Overall 0.00855% 138/1,613,524 alleles · ultra-rare exomes 132/1,461,422 · genomes 6/152,102 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0112%	8,938
Remaining individualsnot grpmax-eligible	0.0048%	20,825
East Asian	0.00223%	44,890
African / African-American	0.00133%	74,926
South Asian	0.0011%	91,032

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.Val310Met
Coding: c.928G>A
MANE Select: NM_001040716
dbSNP: rs145970773
Type: single nucleotide variant
Location: chr11:66868940 (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 310: 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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PC p.Val310= Likely benign ★ same residue
PC p.Ala280Thr Uncertain significance ★★ ⚠ same condition
PC p.Ala431Gly Uncertain significance ★★ ⚠ same condition
PC p.Arg31His Uncertain significance ★★ ⚠ same condition
PC p.Arg385Cys Uncertain significance ★★ ⚠ same condition
PC p.Arg393Cys Uncertain significance ★★ ⚠ same condition
PC p.Arg77Trp Uncertain significance ★★ ⚠ same condition
PC p.Asp1067Asn Uncertain significance ★★ ⚠ same condition

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-val310met (accessed [today's date]).

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