Is KRT1 p.Ser124Arg (c.370A>C) pathogenic?

KRT1 p.Ser124Arg (c.370A>C) is classified Uncertain significance in KRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-10). AlphaMissense: ambiguous (0.5442); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with KRT1 p.Ser124Arg (c.370A>C)?

KRT1 p.Ser124Arg (c.370A>C) is associated with Inborn genetic diseases (ClinVar).

How common is KRT1 p.Ser124Arg (c.370A>C) in the general population?

KRT1 p.Ser124Arg (c.370A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KRT1 p.Ser124Arg (c.370A>C)?

AlphaMissense predicts ambiguous (score 0.5442) — an in-silico prediction, not a clinical call.

KRT1 p.Ser124Arg

c.370A>C · VCV4044768

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5442 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5442	ambiguous
REVEL	0.136	moderately benign-leaning
SaProt	LLR -6.48	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Regional constraint	o/e 0.96	unconstrained · MANE · 5,152 bp · p 0.25 · regional, not allelic
Overall
CADD	11.11	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

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: KRT1
Protein: p.Ser124Arg
Coding: c.370A>C
MANE Select: NM_006121
Type: single nucleotide variant
Location: chr12:52679979 (GRCh38)
Gene constraint: LOEUF 0.7 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.62 · 3 PDB
Residue 124: the 'head' region

Full KRT1 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

KRT1 p.Gln190Lys Uncertain significance ★★ ⚠ same condition
KRT1 p.Gln466Arg Uncertain significance ★★ ⚠ same condition
KRT1 p.Gly585Trp Uncertain significance ★★ same condition
KRT1 p.Val80Met Uncertain significance ★★ same condition
KRT1 p.Ala362Thr Uncertain significance ★ ⚠ same condition
KRT1 p.Ala459Val Uncertain significance ★ same condition
KRT1 p.Arg29His Uncertain significance ★ ⚠ same condition
KRT1 p.Arg37His 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/krt1-p-ser124arg (accessed [today's date]).

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