Is PRKCH p.Pro313Ala (c.937C>G) pathogenic?

PRKCH p.Pro313Ala (c.937C>G) is classified Uncertain significance in PRKCH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-23). AlphaMissense: likely benign (0.1748); Ultra-rare (popmax 0.0111%, eas).

How common is PRKCH p.Pro313Ala (c.937C>G) in the general population?

PRKCH p.Pro313Ala (c.937C>G) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about PRKCH p.Pro313Ala (c.937C>G)?

AlphaMissense predicts likely benign (score 0.1748) — an in-silico prediction, not a clinical call.

PRKCH p.Pro313Ala

c.937C>G · rs753172125 · VCV2458178

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1748 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1748	likely benign
REVEL	0.33	indeterminate
SaProt	LLR -6.78	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 35 kb · p 0.21 · regional, not allelic
Overall
CADD	21.0	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 0.0111% East Asian · 5/44,870 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00031% 5/1,613,300 alleles · ultra-rare exomes 5/1,461,020 · genomes 0/152,280 · 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: PRKCH
Protein: p.Pro313Ala
Coding: c.937C>G
MANE Select: NM_006255
dbSNP: rs753172125
Type: single nucleotide variant
Location: chr14:61453330 (GRCh38)
Gene constraint: LOEUF 0.467 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.75 · 4 PDB

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

Similar variants

PRKCH p.Pro313Ser Uncertain significance ★ ⚠ same residue
PRKCH p.Ile445= Benign ★★ same type
PRKCH c.578+3A>G Uncertain significance ★ same type
PRKCH p.Ala114Val Uncertain significance ★ ⚠ same type
PRKCH p.Ala539Thr Uncertain significance ★ ⚠ same type
PRKCH p.Ala620Val Uncertain significance ★ ⚠ same type
PRKCH p.Arg110Cys Uncertain significance ★ ⚠ same type
PRKCH p.Arg149Trp 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/prkch-p-pro313ala (accessed [today's date]).

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