Is KRT1 p.Ser7Phe (c.20C>T) pathogenic?

KRT1 p.Ser7Phe (c.20C>T) is classified Uncertain significance in KRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). AlphaMissense: ambiguous (0.3573); Absent from gnomAD v4.1.

How common is KRT1 p.Ser7Phe (c.20C>T) in the general population?

KRT1 p.Ser7Phe (c.20C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KRT1 p.Ser7Phe (c.20C>T)?

AlphaMissense predicts ambiguous (score 0.3573) — an in-silico prediction, not a clinical call.

KRT1 p.Ser7Phe

c.20C>T · rs1941567848 · VCV2643033

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3573 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3573	ambiguous
REVEL	0.211	benign-leaning
SaProt	LLR -10.56	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -2.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 5,152 bp · p 0.25 · regional, not allelic
Overall
CADD	20.7	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.Ser7Phe
Coding: c.20C>T
MANE Select: NM_006121
dbSNP: rs1941567848
Type: single nucleotide variant
Location: chr12:52680329 (GRCh38)
Gene constraint: LOEUF 0.7 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.62 · 3 PDB
Residue 7: the 'head' region

Full KRT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KRT1 c.1255-1G>T Pathogenic ★★ same type
KRT1 c.591+1G>C Pathogenic ★★ same type
KRT1 p.Asn188Lys Pathogenic ★★ same type
KRT1 p.Asn188Ser Pathogenic/Likely pathogenic ★★ same type
KRT1 p.Ile195Asn Pathogenic/Likely pathogenic ★★ same type
KRT1 p.Ile479Thr Pathogenic/Likely pathogenic ★★ same type
KRT1 p.Leu187Phe Pathogenic ★★ same type
KRT1 p.Leu485Phe Pathogenic/Likely pathogenic ★★ 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/krt1-p-ser7phe (accessed [today's date]).

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