Is KRT86 p.Cys18= (c.54C>T) pathogenic?

KRT86 p.Cys18= (c.54C>T) is classified Benign in KRT86 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-05). Common (popmax 23.7%, sas) — too common for a highly-penetrant pathogenic allele.

KRT86 p.Cys18=

Q: How common is KRT86 p.Cys18= (c.54C>T) in the general population?

KRT86 p.Cys18= (c.54C>T) is common (popmax 23.7%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.54C>T · rs74651927 · VCV1248361

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 23.7%, sas) — too common for a highly-penetrant pathogenic allele

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 -9.6	GERP -0.24
Overall
CADD	10.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 23.7% South Asian · 21,617/91,086 alleles

Filtering AF 23.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 23.4%

Overall 15.5% 250,585/1,613,500 alleles · common exomes 227,330/1,461,224 · genomes 23,255/152,276 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	25.5%	4
South Asiangrpmax	23.7%	4
African / African-American	16.7%	6
European (non-Finnish)	15.6%	6
Middle Eastern	14.9%	7
Remaining individualsnot grpmax-eligible	14.6%	7
Finnishnot grpmax-eligible	12.7%	8
Admixed American	12.2%	8
East Asian	10%	10
Ashkenazi Jewishnot grpmax-eligible	6.94%	14

Amish 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: KRT86
Protein: p.Cys18=
Coding: c.54C>T
MANE Select: NM_001320198
dbSNP: rs74651927
Type: single nucleotide variant
Location: chr12:52301970 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.50
Residue 18: the 'head' region

Full KRT86 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KRT86 p.Ala293Asp Uncertain significance ★★ ⚠ same type
KRT81 p.Ala359= Benign ★★ same type
KRT86 c.1027-116G>A Benign ★★ same type
KRT86 c.1027-15C>T Likely benign ★★ same type
KRT86 c.1247+36C>A Benign ★★ same type
KRT86 c.1248-152C>T Likely benign ★★ same type
KRT86 c.370-9G>A Likely benign ★★ same type
KRT86 c.578+178G>C Benign ★★ 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/krt86-p-cys18 (accessed [today's date]).

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