Is KRT12 p.Leu239Val (c.715C>G) pathogenic?

KRT12 p.Leu239Val (c.715C>G) is classified Uncertain significance in KRT12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). AlphaMissense: likely benign (0.1698); Ultra-rare (popmax 0.029%, eas); Associated with Inborn genetic diseases.

What condition is associated with KRT12 p.Leu239Val (c.715C>G)?

KRT12 p.Leu239Val (c.715C>G) is associated with Inborn genetic diseases (ClinVar).

How common is KRT12 p.Leu239Val (c.715C>G) in the general population?

KRT12 p.Leu239Val (c.715C>G) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about KRT12 p.Leu239Val (c.715C>G)?

AlphaMissense predicts likely benign (score 0.1698) — an in-silico prediction, not a clinical call.

KRT12 p.Leu239Val

c.715C>G · rs199790779 · VCV3116322

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1698 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1698	likely benign
REVEL	0.705	pathogenic-leaning
SaProt	LLR -10.19	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 5,522 bp · p 0.13 · regional, not allelic
Overall
CADD	24.3	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 0.029% East Asian · 13/44,894 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.000805% 13/1,614,120 alleles · ultra-rare exomes 10/1,461,874 · genomes 3/152,246 · 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: KRT12
Protein: p.Leu239Val
Coding: c.715C>G
MANE Select: NM_000223
dbSNP: rs199790779
Type: single nucleotide variant
Location: chr17:40864898 (GRCh38)
Gene constraint: LOEUF 0.979 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.57
Residue 239: 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.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-leu239val (accessed [today's date]).

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