Is HERC1 p.Ser97Pro (c.289T>C) pathogenic?

HERC1 p.Ser97Pro (c.289T>C) is classified Uncertain significance in HERC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-28). AlphaMissense: likely pathogenic (0.9787); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with HERC1 p.Ser97Pro (c.289T>C)?

HERC1 p.Ser97Pro (c.289T>C) is associated with Inborn genetic diseases (ClinVar).

How common is HERC1 p.Ser97Pro (c.289T>C) in the general population?

HERC1 p.Ser97Pro (c.289T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HERC1 p.Ser97Pro (c.289T>C)?

AlphaMissense predicts likely pathogenic (score 0.9787) — an in-silico prediction, not a clinical call.

HERC1 p.Ser97Pro

c.289T>C · rs1596222539 · VCV2298626

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9787 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9787	likely pathogenic
REVEL	0.313	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 46 kb · p 1.1e-25 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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: HERC1
Protein: p.Ser97Pro
Coding: c.289T>C
MANE Select: NM_003922
dbSNP: rs1596222539
Type: single nucleotide variant
Location: chr15:63775335 (GRCh38)
Gene constraint: LOEUF 0.33 · pLI 1.00 (gnomAD)

Full HERC1 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

HERC1 p.Ala1494Val Uncertain significance ★★ ⚠ same condition
HERC1 p.Ala2289Thr Uncertain significance ★★ ⚠ same condition
HERC1 p.Ala276Glu Uncertain significance ★★ same condition
HERC1 p.Ala2875Val Uncertain significance ★★ ⚠ same condition
HERC1 p.Ala3045Val Uncertain significance ★★ ⚠ same condition
HERC1 p.Ala3598Thr Uncertain significance ★★ ⚠ same condition
HERC1 p.Ala4182Val Uncertain significance ★★ ⚠ same condition
HERC1 p.Arg1298His 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/herc1-p-ser97pro (accessed [today's date]).

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