Is KRT5 p.Ile183Ser (c.548T>G) pathogenic?

KRT5 p.Ile183Ser (c.548T>G) is classified Likely pathogenic in KRT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-22). AlphaMissense: likely pathogenic (0.9986); Absent from gnomAD v4.1.

How common is KRT5 p.Ile183Ser (c.548T>G) in the general population?

KRT5 p.Ile183Ser (c.548T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KRT5 p.Ile183Ser (c.548T>G)?

AlphaMissense predicts likely pathogenic (score 0.9986) — an in-silico prediction, not a clinical call.

KRT5 p.Ile183Ser

c.548T>G · rs267607661 · VCV1502324

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9986 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9986	likely pathogenic ✓ concordant with ClinVar · top 3% in KRT5
REVEL	0.972	strongly pathogenic-leaning
SaProt	LLR -15.24	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.3	phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,321 bp · p 0.7 · regional, not allelic
Overall
CADD	32.0	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: KRT5
Protein: p.Ile183Ser
Coding: c.548T>G
MANE Select: NM_000424
dbSNP: rs267607661
Type: single nucleotide variant
Location: chr12:52519749 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 2 PDB
Residue 183: the if rod domain; a UniProt-annotated variant site (in ddd1); the 'coil 1a' region; a UniProt-annotated variant site (in ebs2a; uncertain significance); a UniProt-annotated variant site (in ebs2d)

Full KRT5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KRT5 p.Ile183Met Pathogenic ★ same residue
KRT5 p.Ile183Thr Likely pathogenic ★ same residue
KRT5 c.555+1G>A Pathogenic ★★ same type
KRT5 p.Ala428Thr Pathogenic/Likely pathogenic ★★ same type
KRT5 p.Ala428Val Pathogenic/Likely pathogenic ★★ same type
KRT5 p.Arg165Ser Pathogenic ★★ same type
KRT5 p.Arg331Cys Pathogenic/Likely pathogenic ★★ same type
KRT5 p.Arg331His 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/krt5-p-ile183ser (accessed [today's date]).

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