Is KRT6C p.Ser541Phe (c.1622C>T) pathogenic?

KRT6C p.Ser541Phe (c.1622C>T) is classified Uncertain significance in KRT6C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-28). AlphaMissense: likely benign (0.1924); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with KRT6C p.Ser541Phe (c.1622C>T)?

KRT6C p.Ser541Phe (c.1622C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KRT6C p.Ser541Phe (c.1622C>T) in the general population?

KRT6C p.Ser541Phe (c.1622C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KRT6C p.Ser541Phe (c.1622C>T)?

AlphaMissense predicts likely benign (score 0.1924) — an in-silico prediction, not a clinical call.

KRT6C p.Ser541Phe

c.1622C>T · VCV4045085

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1924 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1924	likely benign
REVEL	0.43	indeterminate
SaProt	LLR -12.38	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP 0.81
Regional constraint	o/e 0.97	unconstrained · MANE · 3,104 bp · p 0.49 · regional, not allelic
Overall
CADD	18.59	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: KRT6C
Protein: p.Ser541Phe
Coding: c.1622C>T
MANE Select: NM_173086
Type: single nucleotide variant
Location: chr12:52469135 (GRCh38)
Gene constraint: LOEUF 1.34 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.63
Residue 541: the 'tail' region

Full KRT6C 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

KRT6C p.Arg260Cys Uncertain significance ★★ ⚠ same condition
KRT6C p.Arg349Trp Uncertain significance ★★ ⚠ same condition
KRT6C p.Arg466Cys Uncertain significance ★★ ⚠ same condition
KRT6C p.Asp331His Uncertain significance ★★ ⚠ same condition
KRT6C p.Glu479Lys Uncertain significance ★★ same condition
KRT6C p.Gly504Ser Uncertain significance ★★ ⚠ same condition
KRT6C p.Gly525Ser Uncertain significance ★★ ⚠ same condition
KRT6C p.Gly57Arg 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/krt6c-p-ser541phe (accessed [today's date]).

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