Is KRT85 p.Ser275Pro (c.823T>C) pathogenic?

KRT85 p.Ser275Pro (c.823T>C) is classified Uncertain significance in KRT85 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-27). AlphaMissense: likely pathogenic (0.9555); Absent from gnomAD v4.1; Associated with ectodermal dysplasia 4, hair/nail type.

What condition is associated with KRT85 p.Ser275Pro (c.823T>C)?

KRT85 p.Ser275Pro (c.823T>C) is associated with ectodermal dysplasia 4, hair/nail type (ClinVar).

How common is KRT85 p.Ser275Pro (c.823T>C) in the general population?

KRT85 p.Ser275Pro (c.823T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KRT85 p.Ser275Pro (c.823T>C)?

AlphaMissense predicts likely pathogenic (score 0.9555) — an in-silico prediction, not a clinical call.

KRT85 p.Ser275Pro

c.823T>C · rs1592141626 · VCV638425

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9555 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ectodermal dysplasia 4, hair/nail type

Computational evidence

Protein change
AlphaMissense	0.9555	likely pathogenic · top 7% in KRT85
REVEL	0.744	pathogenic-leaning
SaProt	LLR -11.12	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 7.1	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 6,136 bp · p 0.65 · regional, not allelic
Overall
CADD	26.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KRT85
Protein: p.Ser275Pro
Coding: c.823T>C
MANE Select: NM_002283
dbSNP: rs1592141626
Type: single nucleotide variant
Location: chr12:52363374 (GRCh38)
Gene constraint: LOEUF 0.89 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.09
Residue 275: the if rod domain; the 'linker 12' region

Full KRT85 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ectodermal dysplasia 4, hair/nail type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KRT85 p.Ser275= Likely benign same residue
KRT85 p.Arg78His Benign/Likely benign ★★ same condition
KRT85 p.Arg180Trp Uncertain significance ★ ⚠ same condition
KRT85 p.Pro483fs Pathogenic same condition
KRT85 p.Arg142His Uncertain significance ★★ ⚠ same type
KRT85 p.Arg315His Uncertain significance ★★ ⚠ same type
KRT85 p.Arg465His Uncertain significance ★★ ⚠ same type
KRT85 p.Asn115Lys Uncertain significance ★★ ⚠ 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/krt85-p-ser275pro (accessed [today's date]).

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