Is KRT4 p.Ser34Pro (c.100T>C) pathogenic?

KRT4 p.Ser34Pro (c.100T>C) is classified Uncertain significance in KRT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely benign (0.1346); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with KRT4 p.Ser34Pro (c.100T>C)?

KRT4 p.Ser34Pro (c.100T>C) is associated with Inborn genetic diseases (ClinVar).

How common is KRT4 p.Ser34Pro (c.100T>C) in the general population?

KRT4 p.Ser34Pro (c.100T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KRT4 p.Ser34Pro (c.100T>C)?

AlphaMissense predicts likely benign (score 0.1346) — an in-silico prediction, not a clinical call.

KRT4 p.Ser34Pro

c.100T>C · VCV4094979

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1346 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1346	likely benign
REVEL	0.486	indeterminate
SaProt	LLR -11.03	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.76, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 6,986 bp · p 0.83 · 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

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: KRT4
Protein: p.Ser34Pro
Coding: c.100T>C
MANE Select: NM_002272
Type: single nucleotide variant
Location: chr12:52813959 (GRCh38)
Gene constraint: LOEUF 1.089 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.77
Residue 34: the 'head' region

Full KRT4 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

KRT4 p.Ala106Gly Uncertain significance ★★ ⚠ same condition
KRT4 p.Asp153Asn Uncertain significance ★★ ⚠ same condition
KRT4 p.Asp247Glu Uncertain significance ★★ same condition
KRT4 p.His398Tyr Likely benign ★★ same condition
KRT4 p.Ala106Thr Uncertain significance ★ ⚠ same condition
KRT4 p.Ala20Asp Uncertain significance ★ ⚠ same condition
KRT4 p.Ala278Glu Uncertain significance ★ ⚠ same condition
KRT4 p.Ala278Val 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/krt4-p-ser34pro (accessed [today's date]).

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