Is KRT86 p.Ser473Phe (c.1418C>T) pathogenic?

KRT86 p.Ser473Phe (c.1418C>T) is classified Uncertain significance in KRT86 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-14). AlphaMissense: likely benign (0.0899); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KRT86 p.Ser473Phe (c.1418C>T)?

KRT86 p.Ser473Phe (c.1418C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KRT86 p.Ser473Phe (c.1418C>T) in the general population?

KRT86 p.Ser473Phe (c.1418C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about KRT86 p.Ser473Phe (c.1418C>T)?

AlphaMissense predicts likely benign (score 0.0899) — an in-silico prediction, not a clinical call.

KRT86 p.Ser473Phe

c.1418C>T · rs763879273 · VCV3116780

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0899 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0899	likely benign
REVEL	0.318	indeterminate
SaProt	LLR -10.52	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -0.88, phastCons 0.94
Regional constraint	o/e 1.06	unconstrained · MANE · 5,286 bp · p 0.28 · regional, not allelic
Overall
CADD	14.85	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,826 alleles

Overall 6.24e-05% 1/1,601,520 alleles · very rare exomes 1/1,449,144 · genomes 0/152,376 · joint denominator

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.Ser473Phe
Coding: c.1418C>T
MANE Select: NM_001320198
dbSNP: rs763879273
Type: single nucleotide variant
Location: chr12:52308542 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.50
Residue 473: the 'tail' 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.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
KRT86 p.Arg21Pro Uncertain significance ★ ⚠ same condition
KRT86 p.Arg221His 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-ser473phe (accessed [today's date]).

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