Is KRT5 p.Ile233= (c.699C>T) pathogenic?

KRT5 p.Ile233= (c.699C>T) is classified Likely benign in KRT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-11). Very rare (popmax 0.00267%, afr).

How common is KRT5 p.Ile233= (c.699C>T) in the general population?

KRT5 p.Ile233= (c.699C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

KRT5 p.Ile233=

c.699C>T · VCV4916989

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.021	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.025
Overall
CADD	6.988	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,890 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00155% 25/1,613,978 alleles · very rare exomes 21/1,461,880 · genomes 4/152,098 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00469%	21,338
African / African-Americangrpmax	0.00267%	37,445
South Asian	0.0022%	45,541
European (non-Finnish)	0.00153%	65,557

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: KRT5
Protein: p.Ile233=
Coding: c.699C>T
MANE Select: NM_000424
Type: single nucleotide variant
Location: chr12:52519017 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 68.86 · 2 PDB
Residue 233: the if rod domain; a UniProt-annotated variant site (in ddd1); the 'coil 1b' region

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

Similar variants

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
KRT5 p.Asn176Ser Pathogenic/Likely pathogenic ★★ same type
KRT5 p.Asn177Ser 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-ile233 (accessed [today's date]).

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