Is KRT12 p.Thr243Pro (c.727A>C) pathogenic?

KRT12 p.Thr243Pro (c.727A>C) is classified Uncertain significance in KRT12 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-17). AlphaMissense: likely pathogenic (0.7744); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with KRT12 p.Thr243Pro (c.727A>C)?

KRT12 p.Thr243Pro (c.727A>C) is associated with Inborn genetic diseases (ClinVar).

How common is KRT12 p.Thr243Pro (c.727A>C) in the general population?

KRT12 p.Thr243Pro (c.727A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KRT12 p.Thr243Pro (c.727A>C)?

AlphaMissense predicts likely pathogenic (score 0.7744) — an in-silico prediction, not a clinical call.

KRT12 p.Thr243Pro

c.727A>C · VCV4840057

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7744 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7744	likely pathogenic · top 7% in KRT12
REVEL	0.829	moderately pathogenic-leaning
SaProt	LLR -15.52	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 4.1	GERP -0.54, 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

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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KRT12
Protein: p.Thr243Pro
Coding: c.727A>C
MANE Select: NM_000223
Type: single nucleotide variant
Location: chr17:40864886 (GRCh38)
Gene constraint: LOEUF 0.979 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.57
Residue 243: 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.Thr243Ile Likely benign ★★ same residue
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

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-thr243pro (accessed [today's date]).

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