Is KRT12 p.Asp213Tyr (c.637G>T) pathogenic?

KRT12 p.Asp213Tyr (c.637G>T) is classified Uncertain significance in KRT12 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-03). AlphaMissense: likely pathogenic (0.7489); Ultra-rare (popmax 0.033%, mid); Associated with Inborn genetic diseases.

What condition is associated with KRT12 p.Asp213Tyr (c.637G>T)?

KRT12 p.Asp213Tyr (c.637G>T) is associated with Inborn genetic diseases (ClinVar).

How common is KRT12 p.Asp213Tyr (c.637G>T) in the general population?

KRT12 p.Asp213Tyr (c.637G>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about KRT12 p.Asp213Tyr (c.637G>T)?

AlphaMissense predicts likely pathogenic (score 0.7489) — an in-silico prediction, not a clinical call.

KRT12 p.Asp213Tyr

c.637G>T · VCV3535823

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7489 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7489	likely pathogenic · top 8% in KRT12
REVEL	0.795	moderately pathogenic-leaning
SaProt	LLR -16.99	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 4.8	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 5,522 bp · p 0.13 · regional, not allelic
Overall
CADD	27.7	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00167% 27/1,613,972 alleles · ultra-rare exomes 27/1,461,670 · genomes 0/152,302 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
South Asian	0.0165%	6,072
Remaining individualsnot grpmax-eligible	0.0032%	31,252
European (non-Finnish)	0.000678%	147,482

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.Asp213Tyr
Coding: c.637G>T
MANE Select: NM_000223
Type: single nucleotide variant
Location: chr17:40866168 (GRCh38)
Gene constraint: LOEUF 0.979 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.57
Residue 213: the if rod domain; the 'coil 1b' 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.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
KRT12 p.Ala35Pro 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-asp213tyr (accessed [today's date]).

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