Is KRT12 p.Met301Thr (c.902T>C) pathogenic?

KRT12 p.Met301Thr (c.902T>C) is classified Likely benign in KRT12 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-12). AlphaMissense: likely pathogenic (0.713); Rare (popmax 0.339%, nfe).

How common is KRT12 p.Met301Thr (c.902T>C) in the general population?

KRT12 p.Met301Thr (c.902T>C) is rare (popmax 0.339%, nfe) (gnomAD).

What do computational predictors say about KRT12 p.Met301Thr (c.902T>C)?

AlphaMissense predicts likely pathogenic (score 0.713) — an in-silico prediction, not a clinical call.

KRT12 p.Met301Thr

c.902T>C · rs139647784 · VCV723635

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.713 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.339%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.713	likely pathogenic · top 10% in KRT12
REVEL	0.814	moderately pathogenic-leaning
SaProt	LLR -11.75	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 6.9	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 5,522 bp · p 0.13 · regional, not allelic
Overall
CADD	24.5	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 0.339% European (non-Finnish) · 4,004/1,179,994 alleles

Filtering AF 0.331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.327%

Overall 0.272% 4,380/1,613,058 alleles · rare exomes 4,130/1,460,820 · genomes 250/152,238 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.339%	295
Finnishnot grpmax-eligible	0.234%	427
Remaining individualsnot grpmax-eligible	0.228%	440
Admixed American	0.0733%	1,364
African / African-American	0.0467%	2,143
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
South Asian	0.0022%	45,517

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: KRT12
Protein: p.Met301Thr
Coding: c.902T>C
MANE Select: NM_000223
dbSNP: rs139647784
Type: single nucleotide variant
Location: chr17:40863770 (GRCh38)
Gene constraint: LOEUF 0.979 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.57
Residue 301: the if rod domain; the 'coil 2' region

Full KRT12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KRT12 p.Met129Val Pathogenic/Likely pathogenic ★★ same type
KRT12 p.Asp213Tyr Uncertain significance ★★ ⚠ same type
KRT12 p.Gln486Glu Uncertain significance ★★ ⚠ same type
KRT12 p.Ile195Phe Uncertain significance ★★ ⚠ same type
KRT12 p.Val228Ile Uncertain significance ★★ ⚠ same type
KRT12 c.808-17T>A Benign/Likely benign ★★ same type
KRT12 p.Arg20Trp Benign ★★ ⚠ same type
KRT12 p.Gln475Arg Likely benign ★★ ⚠ 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/krt12-p-met301thr (accessed [today's date]).

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