Is KRT6A p.Arg232= (c.696G>C) pathogenic?

KRT6A p.Arg232= (c.696G>C) is classified Likely benign in KRT6A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-15). Very rare (popmax 0.00119%, nfe).

How common is KRT6A p.Arg232= (c.696G>C) in the general population?

KRT6A p.Arg232= (c.696G>C) is very rare (popmax 0.00119%, nfe) (gnomAD).

KRT6A p.Arg232=

c.696G>C · rs766998826 · VCV2985939

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -1.7
Overall
CADD	1.498	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,180,020 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00105% 17/1,614,016 alleles · very rare exomes 16/1,461,894 · genomes 1/152,122 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)grpmax	0.00119%	84,287

Ashkenazi Jewish 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: KRT6A
Protein: p.Arg232=
Coding: c.696G>C
MANE Select: NM_005554
dbSNP: rs766998826
Type: single nucleotide variant
Location: chr12:52491581 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.16 · 1 PDB
Residue 232: the if rod domain; the 'coil 1b' region

Full KRT6A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KRT6A p.Arg232Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
KRT6A p.Arg232Trp Uncertain significance ★ ⚠ same residue
KRT6A c.1460-1G>C Pathogenic/Likely pathogenic ★★ same type
KRT6A p.Arg164Cys Pathogenic/Likely pathogenic ★★ same type
KRT6A p.Asn171Lys Pathogenic ★★ same type
KRT6A p.Asn171Ser Pathogenic ★★ same type
KRT6A p.Glu163Lys Pathogenic ★★ same type
KRT6A p.Glu472Lys 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/krt6a-p-arg232 (accessed [today's date]).

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