Is KRT12 p.Gly291Val (c.872G>T) pathogenic?

KRT12 p.Gly291Val (c.872G>T) is classified Uncertain significance in KRT12 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-25). AlphaMissense: ambiguous (0.4881); Very rare (popmax 0.0028%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KRT12 p.Gly291Val (c.872G>T)?

KRT12 p.Gly291Val (c.872G>T) is associated with Inborn genetic diseases (ClinVar).

How common is KRT12 p.Gly291Val (c.872G>T) in the general population?

KRT12 p.Gly291Val (c.872G>T) is very rare (popmax 0.0028%, nfe) (gnomAD).

What do computational predictors say about KRT12 p.Gly291Val (c.872G>T)?

AlphaMissense predicts ambiguous (score 0.4881) — an in-silico prediction, not a clinical call.

KRT12 p.Gly291Val

c.872G>T · rs780612518 · VCV2290991

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4881 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0028%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4881	ambiguous
REVEL	0.47	indeterminate
SaProt	LLR -10.67	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 5,522 bp · p 0.13 · regional, not allelic
Overall
CADD	26.2	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 0.0028% European (non-Finnish) · 33/1,179,902 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00211% 34/1,612,348 alleles · very rare exomes 32/1,460,192 · genomes 2/152,156 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0028%	35,755
Remaining individualsnot grpmax-eligible	0.0016%	62,330

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.Gly291Val
Coding: c.872G>T
MANE Select: NM_000223
dbSNP: rs780612518
Type: single nucleotide variant
Location: chr17:40863800 (GRCh38)
Gene constraint: LOEUF 0.979 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.57
Residue 291: the if rod domain; the 'linker 12' region

Full KRT12 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

KRT12 p.Met129Val Pathogenic/Likely pathogenic ★★ same condition
KRT12 p.Asp213Tyr Uncertain significance ★★ ⚠ same condition
KRT12 p.Gln486Glu Uncertain significance ★★ ⚠ same condition
KRT12 p.Ile195Phe Uncertain significance ★★ ⚠ same condition
KRT12 p.Val228Ile Uncertain significance ★★ ⚠ same condition
KRT12 p.Ala149Val Uncertain significance ★ ⚠ same condition
KRT12 p.Ala171Thr Uncertain significance ★ ⚠ same condition
KRT12 p.Ala207Val 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/krt12-p-gly291val (accessed [today's date]).

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