Is KRT6A p.Val229= (c.687C>T) pathogenic?

KRT6A p.Val229= (c.687C>T) is classified Benign in KRT6A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). Ultra-rare (popmax 0.0623%, nfe).

How common is KRT6A p.Val229= (c.687C>T) in the general population?

KRT6A p.Val229= (c.687C>T) is ultra-rare (popmax 0.0623%, nfe) (gnomAD).

KRT6A p.Val229=

c.687C>T · rs201950477 · VCV2045050

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0623%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3.8
Overall
CADD	0.107	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0623% European (non-Finnish) · 735/1,179,932 alleles

Filtering AF 0.0585% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.057%

Overall 0.0557% 898/1,611,010 alleles · ultra-rare exomes 829/1,460,244 · genomes 69/150,766 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.156%	643
European (non-Finnish)grpmax	0.0623%	1,605
Remaining individualsnot grpmax-eligible	0.0593%	1,685
Admixed American	0.0522%	1,915
Finnishnot grpmax-eligible	0.036%	2,778
Middle Eastern	0.0329%	3,042
South Asian	0.0143%	6,998
African / African-American	0.0134%	7,483
East Asian	0.00232%	43,104

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.Val229=
Coding: c.687C>T
MANE Select: NM_005554
dbSNP: rs201950477
Type: single nucleotide variant
Location: chr12:52491590 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.16 · 1 PDB
Residue 229: 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 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
KRT6A p.Ile462Asn Pathogenic/Likely pathogenic ★★ same type
KRT6A p.Leu170Phe 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-val229 (accessed [today's date]).

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