Is KRT86 p.Arg33= (c.99T>C) pathogenic?

KRT86 p.Arg33= (c.99T>C) is classified Likely benign in KRT86 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-27). Very rare (popmax 0.0066%, sas); Associated with Inborn genetic diseases.

What condition is associated with KRT86 p.Arg33= (c.99T>C)?

KRT86 p.Arg33= (c.99T>C) is associated with Inborn genetic diseases (ClinVar).

How common is KRT86 p.Arg33= (c.99T>C) in the general population?

KRT86 p.Arg33= (c.99T>C) is very rare (popmax 0.0066%, sas) (gnomAD).

KRT86 p.Arg33=

c.99T>C · VCV3865745

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0066%, sas)

Conditions

Inborn genetic diseases

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 -13	GERP -3.8
Overall
CADD	4.388	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0066% South Asian · 6/90,966 alleles

Filtering AF 0.00287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00298% 48/1,611,612 alleles · very rare exomes 44/1,459,644 · genomes 4/151,968 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0066%	15,161
Remaining individualsnot grpmax-eligible	0.00321%	31,183
European (non-Finnish)	0.00314%	31,864
African / African-American	0.00267%	37,393
East Asian	0.00223%	44,816

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.Arg33=
Coding: c.99T>C
MANE Select: NM_001320198
Type: single nucleotide variant
Location: chr12:52302015 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.50
Residue 33: the 'head' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KRT86 p.Arg33Cys Uncertain significance ★ ⚠ same residue
KRT86 p.Arg33Leu Uncertain significance ★ same residue
KRT86 p.Ala293Asp Uncertain significance ★★ ⚠ same condition
KRT86 p.Ala218Thr Uncertain significance ★ ⚠ same condition
KRT86 p.Ala360Ser Uncertain significance ★ ⚠ same condition
KRT86 p.Ala383Asp Uncertain significance ★ ⚠ same condition
KRT86 p.Ala404Thr Uncertain significance ★ ⚠ same condition
KRT86 p.Ala446Asp Uncertain significance ★ ⚠ same condition

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-arg33 (accessed [today's date]).

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