Is KRT12 p.Gly325Arg (c.973G>A) pathogenic?

KRT12 p.Gly325Arg (c.973G>A) is classified Uncertain significance in KRT12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-16). AlphaMissense: likely benign (0.1549); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with KRT12 p.Gly325Arg (c.973G>A)?

KRT12 p.Gly325Arg (c.973G>A) is associated with Inborn genetic diseases (ClinVar).

How common is KRT12 p.Gly325Arg (c.973G>A) in the general population?

KRT12 p.Gly325Arg (c.973G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about KRT12 p.Gly325Arg (c.973G>A)?

AlphaMissense predicts likely benign (score 0.1549) — an in-silico prediction, not a clinical call.

KRT12 p.Gly325Arg

c.973G>A · VCV3865385

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1549 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1549	likely benign
REVEL	0.16	moderately benign-leaning
SaProt	LLR -13.13	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.36	acceptor gain · deltas
Pangolin	Δ0.21	gain · loss 0.10 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.58	GERP -0.79
Regional constraint	o/e 0.94	unconstrained · MANE · 5,522 bp · p 0.13 · regional, not allelic
Overall
CADD	19.01	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 0.00167% Admixed American · 1/60,014 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000867% 14/1,614,106 alleles · very rare exomes 11/1,461,888 · genomes 3/152,218 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,014
European (non-Finnish)	0.0011%	90,773

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.Gly325Arg
Coding: c.973G>A
MANE Select: NM_000223
Type: single nucleotide variant
Location: chr17:40863607 (GRCh38)
Gene constraint: LOEUF 0.979 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.57
Residue 325: the if rod domain; the 'coil 2' 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-gly325arg (accessed [today's date]).

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