Is KRT86 p.Ala351= (c.1053T>C) pathogenic?

KRT86 p.Ala351= (c.1053T>C) is classified Benign/Likely benign in KRT86 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-02-14). Low-frequency (popmax 3.96%, afr); Associated with monilethrix.

What condition is associated with KRT86 p.Ala351= (c.1053T>C)?

KRT86 p.Ala351= (c.1053T>C) is associated with monilethrix (ClinVar).

How common is KRT86 p.Ala351= (c.1053T>C) in the general population?

KRT86 p.Ala351= (c.1053T>C) is low-frequency (popmax 3.96%, afr) (gnomAD).

How is Monilethrix inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

KRT86 p.Ala351=

c.1053T>C · rs28733260 · VCV768545

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.96%, afr)

Conditions

monilethrix

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 -1.3	GERP -3.1
Overall
CADD	8.687	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.96% African / African-American · 2,962/74,860 alleles

Filtering AF 3.84% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.79%

Overall 0.222% 3,581/1,613,810 alleles · low-frequency exomes 1,880/1,461,584 · genomes 1,701/152,226 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.96%	25
Remaining individualsnot grpmax-eligible	0.285%	351
Middle Eastern	0.269%	372
Admixed American	0.253%	395
South Asian	0.0231%	4,337
European (non-Finnish)	0.0212%	4,720
East Asian	0.00446%	22,436

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.Ala351=
Coding: c.1053T>C
MANE Select: NM_001320198
dbSNP: rs28733260
Type: single nucleotide variant
Location: chr12:52306086 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.50
Residue 351: the if rod domain; the 'coil 2' region

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

Disease context

monilethrix — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Monilethrix (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

KRT86 p.Asn228= Benign/Likely benign ★★ same condition
KRT86 p.Leu368= Benign/Likely benign ★★ same condition
KRT86 p.Glu402Lys Likely pathogenic ★ same condition
KRT86 p.Glu413Lys Pathogenic ★ same condition
KRT86 p.Ala118Glu Pathogenic same condition
KRT86 p.Asn114Asp Pathogenic same condition
KRT86 p.Glu402Gln Pathogenic same condition
KRT86 p.Glu413Asp Pathogenic 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-ala351 (accessed [today's date]).

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