Is KRT86 p.Ala293Asp (c.878C>A) pathogenic?

KRT86 p.Ala293Asp (c.878C>A) is classified Uncertain significance in KRT86 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-15). AlphaMissense: likely pathogenic (0.8312); Ultra-rare (popmax 0.0187%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KRT86 p.Ala293Asp (c.878C>A)?

KRT86 p.Ala293Asp (c.878C>A) is associated with Inborn genetic diseases (ClinVar).

How common is KRT86 p.Ala293Asp (c.878C>A) in the general population?

KRT86 p.Ala293Asp (c.878C>A) is ultra-rare (popmax 0.0187%, nfe) (gnomAD).

What do computational predictors say about KRT86 p.Ala293Asp (c.878C>A)?

AlphaMissense predicts likely pathogenic (score 0.8312) — an in-silico prediction, not a clinical call.

KRT86 p.Ala293Asp

c.878C>A · rs376319970 · VCV2324352

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8312 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8312	likely pathogenic
REVEL	0.922	moderately pathogenic-leaning
SaProt	LLR -14.50	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 1.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 5,286 bp · p 0.28 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% European (non-Finnish) · 221/1,180,052 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0159%

Overall 0.0144% 233/1,614,108 alleles · ultra-rare exomes 219/1,461,876 · genomes 14/152,232 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0187%	5,340
Remaining individualsnot grpmax-eligible	0.0096%	10,414
Admixed American	0.00667%	15,002
African / African-American	0.00267%	37,463

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.Ala293Asp
Coding: c.878C>A
MANE Select: NM_001320198
dbSNP: rs376319970
Type: single nucleotide variant
Location: chr12:52305382 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.50
Residue 293: the if rod domain; the 'coil 2' 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.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
KRT86 p.Arg21Pro Uncertain significance ★ ⚠ same condition
KRT86 p.Arg221His Uncertain significance ★ ⚠ same condition
KRT86 p.Arg241Gln 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-ala293asp (accessed [today's date]).

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