Is KRT17 p.Ser4Phe (c.11C>T) pathogenic?

KRT17 p.Ser4Phe (c.11C>T) is classified Uncertain significance in KRT17 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-09). AlphaMissense: likely benign (0.2663); Very rare (popmax 0.00334%, amr); Associated with Inborn genetic diseases.

What condition is associated with KRT17 p.Ser4Phe (c.11C>T)?

KRT17 p.Ser4Phe (c.11C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KRT17 p.Ser4Phe (c.11C>T) in the general population?

KRT17 p.Ser4Phe (c.11C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about KRT17 p.Ser4Phe (c.11C>T)?

AlphaMissense predicts likely benign (score 0.2663) — an in-silico prediction, not a clinical call.

KRT17 p.Ser4Phe

c.11C>T · VCV3535857

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2663 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2663	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -10.63	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 4,912 bp · p 0.082 · regional, not allelic
Overall
CADD	24.2	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 0.00334% Admixed American · 2/59,942 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,610,142 alleles · very rare exomes 2/1,457,818 · genomes 0/152,324 · joint denominator

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: KRT17
Protein: p.Ser4Phe
Coding: c.11C>T
MANE Select: NM_000422
Type: single nucleotide variant
Location: chr17:41624499 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.28
Residue 4: the 'head' region; the 'disordered' region

Full KRT17 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

KRT17 p.Ser4Thr Benign ★★ same residue
KRT17 p.Arg406Cys Uncertain significance ★★ ⚠ same condition
KRT17 p.Ala178Pro Uncertain significance ★ ⚠ same condition
KRT17 p.Ala354Asp Uncertain significance ★ ⚠ same condition
KRT17 p.Arg251Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
KRT17 p.Arg257His Uncertain significance ★ ⚠ same condition
KRT17 p.Asp118Glu Uncertain significance ★ ⚠ same condition
KRT17 p.Asp195Glu 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/krt17-p-ser4phe (accessed [today's date]).

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