Is KRT17 p.Ala178Pro (c.532G>C) pathogenic?

KRT17 p.Ala178Pro (c.532G>C) is classified Uncertain significance in KRT17 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-11). AlphaMissense: likely pathogenic (0.9611); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with KRT17 p.Ala178Pro (c.532G>C)?

KRT17 p.Ala178Pro (c.532G>C) is associated with Inborn genetic diseases (ClinVar).

How common is KRT17 p.Ala178Pro (c.532G>C) in the general population?

KRT17 p.Ala178Pro (c.532G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KRT17 p.Ala178Pro (c.532G>C)?

AlphaMissense predicts likely pathogenic (score 0.9611) — an in-silico prediction, not a clinical call.

KRT17 p.Ala178Pro

c.532G>C · VCV3535859

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9611 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9611	likely pathogenic · top 9% in KRT17
REVEL	0.689	pathogenic-leaning
SaProt	LLR -11.94	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.24	GERP -3.7, phastCons 0.97
Regional constraint	o/e 0.93	unconstrained · MANE · 4,912 bp · p 0.082 · regional, not allelic
Overall
CADD	23.1	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: KRT17
Protein: p.Ala178Pro
Coding: c.532G>C
MANE Select: NM_000422
Type: single nucleotide variant
Location: chr17:41622495 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.28
Residue 178: the if rod domain; the 'coil 1b' region

Full KRT17 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

KRT17 p.Arg406Cys Uncertain significance ★★ ⚠ same condition
KRT17 p.Ala354Asp Uncertain significance ★ ⚠ same condition
KRT17 p.Arg251Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
KRT17 p.Arg257His Uncertain significance ★ ⚠ same condition
KRT17 p.Asp118Glu Uncertain significance ★ ⚠ same condition
KRT17 p.Asp195Glu Uncertain significance ★ ⚠ same condition
KRT17 p.Gln315Arg Uncertain significance ★ ⚠ same condition
KRT17 p.Glu213Asp 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/krt17-p-ala178pro (accessed [today's date]).

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