Is KRT12 p.Gly54Arg (c.160G>A) pathogenic?

KRT12 p.Gly54Arg (c.160G>A) is classified Benign in KRT12 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-06). AlphaMissense: likely benign (0.1316); Rare (popmax 0.174%, eas); Associated with KRT12-related disorder.

What condition is associated with KRT12 p.Gly54Arg (c.160G>A)?

KRT12 p.Gly54Arg (c.160G>A) is associated with KRT12-related disorder (ClinVar).

How common is KRT12 p.Gly54Arg (c.160G>A) in the general population?

KRT12 p.Gly54Arg (c.160G>A) is rare (popmax 0.174%, eas) (gnomAD).

What do computational predictors say about KRT12 p.Gly54Arg (c.160G>A)?

AlphaMissense predicts likely benign (score 0.1316) — an in-silico prediction, not a clinical call.

KRT12 p.Gly54Arg

c.160G>A · rs141949869 · VCV3048993

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1316 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.174%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

KRT12-related disorder

Computational evidence

Protein change
AlphaMissense	0.1316	likely benign
REVEL	0.249	benign-leaning
SaProt	LLR -9.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 2, phastCons 0.003
Regional constraint	o/e 0.94	unconstrained · MANE · 5,522 bp · p 0.13 · regional, not allelic
Overall
CADD	17.47	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 0.174% East Asian · 78/44,722 alleles

Filtering AF 0.143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.132%

Overall 0.00774% 124/1,601,866 alleles · rare exomes 110/1,449,568 · genomes 14/152,298 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.174%	573
Remaining individualsnot grpmax-eligible	0.0597%	1,674
Admixed American	0.00171%	58,322
Finnishnot grpmax-eligible	0.00157%	63,694
African / African-American	0.00134%	74,596
European (non-Finnish)	0.000511%	195,616

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.Gly54Arg
Coding: c.160G>A
MANE Select: NM_000223
dbSNP: rs141949869
Type: single nucleotide variant
Location: chr17:40867027 (GRCh38)
Gene constraint: LOEUF 0.979 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.57
Residue 54: the 'head' region

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

Disease context

KRT12-related disorder

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-gly54arg (accessed [today's date]).

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