Is KRT12 p.Asp248Asn (c.742G>A) pathogenic?

KRT12 p.Asp248Asn (c.742G>A) is classified Uncertain significance in KRT12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-30). AlphaMissense: likely benign (0.2084); Ultra-rare (popmax 0.0413%, afr).

How common is KRT12 p.Asp248Asn (c.742G>A) in the general population?

KRT12 p.Asp248Asn (c.742G>A) is ultra-rare (popmax 0.0413%, afr) (gnomAD).

What do computational predictors say about KRT12 p.Asp248Asn (c.742G>A)?

AlphaMissense predicts likely benign (score 0.2084) — an in-silico prediction, not a clinical call.

KRT12 p.Asp248Asn

c.742G>A · rs150674571 · VCV2076233

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2084 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0413%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2084	likely benign
REVEL	0.574	indeterminate
SaProt	LLR -11.75	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP 1.1, phastCons 0.99
Regional constraint	o/e 0.94	unconstrained · MANE · 5,522 bp · p 0.13 · regional, not allelic
Overall
CADD	23.5	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 0.0413% African / African-American · 31/75,056 alleles

Filtering AF 0.0298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.026%

Overall 0.00403% 65/1,614,222 alleles · ultra-rare exomes 37/1,461,876 · genomes 28/152,346 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0413%	2,421
Admixed American	0.0167%	6,003
Middle Eastern	0.0165%	6,060
East Asian	0.00891%	11,223
Remaining individualsnot grpmax-eligible	0.0064%	15,626
European (non-Finnish)	0.00119%	84,288
South Asian	0.0011%	91,090

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.Asp248Asn
Coding: c.742G>A
MANE Select: NM_000223
dbSNP: rs150674571
Type: single nucleotide variant
Location: chr17:40864871 (GRCh38)
Gene constraint: LOEUF 0.979 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.57
Residue 248: the if rod domain; a UniProt-annotated variant site (in mecd1; uncertain significance); the 'coil 1b' region

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

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-asp248asn (accessed [today's date]).

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