Is KRT85 p.Ser275= (c.825G>A) pathogenic?

KRT85 p.Ser275= (c.825G>A) is classified Likely benign in KRT85 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-05-09). Very rare (popmax 0.0011%, nfe); Associated with KRT85-related disorder.

What condition is associated with KRT85 p.Ser275= (c.825G>A)?

KRT85 p.Ser275= (c.825G>A) is associated with KRT85-related disorder (ClinVar).

How common is KRT85 p.Ser275= (c.825G>A) in the general population?

KRT85 p.Ser275= (c.825G>A) is very rare (popmax 0.0011%, nfe) (gnomAD).

KRT85 p.Ser275=

c.825G>A · VCV3346732

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Conditions

KRT85-related disorder

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 -20	GERP -3.9
Overall
CADD	2.464	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,180,042 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000929% 15/1,613,996 alleles · very rare exomes 14/1,461,894 · genomes 1/152,102 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,243
European (non-Finnish)grpmax	0.0011%	90,772

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: KRT85
Protein: p.Ser275=
Coding: c.825G>A
MANE Select: NM_002283
Type: single nucleotide variant
Location: chr12:52363372 (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

KRT85-related disorder

Similar variants

KRT85 p.Ser275Pro Uncertain significance ★ ⚠ same residue
KRT85 c.630-21C>T Benign same condition
KRT85 c.691-6G>C Likely benign same condition
KRT85 p.Arg265= Likely benign same condition
KRT85 p.Ser5= Likely benign same condition
KRT85 p.Thr462= Likely benign same condition
KRT85 p.Arg142His Uncertain significance ★★ ⚠ same type
KRT85 p.Arg315His 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-ser275 (accessed [today's date]).

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