Is WHRN p.Ser101Phe (c.302C>T) pathogenic?

WHRN p.Ser101Phe (c.302C>T) is classified Uncertain significance in WHRN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-21). AlphaMissense: likely pathogenic (0.9754); Very rare (popmax 8.48e-05%, nfe).

How common is WHRN p.Ser101Phe (c.302C>T) in the general population?

WHRN p.Ser101Phe (c.302C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about WHRN p.Ser101Phe (c.302C>T)?

AlphaMissense predicts likely pathogenic (score 0.9754) — an in-silico prediction, not a clinical call.

WHRN p.Ser101Phe

c.302C>T · rs780852792 · VCV3233838

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9754 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9754	likely pathogenic · top 6% in WHRN
REVEL	0.427	indeterminate
SaProt	LLR -5.93	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 102 kb · p 0.96 · regional, not allelic
Overall
CADD	33.0	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) · 1/1,179,790 alleles

Overall 6.21e-05% 1/1,609,230 alleles · very rare exomes 1/1,456,846 · genomes 0/152,384 · 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: WHRN
Protein: p.Ser101Phe
Coding: c.302C>T
MANE Select: NM_015404
dbSNP: rs780852792
Type: single nucleotide variant
Location: chr9:114504500 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 59.39 · 5 PDB

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

Similar variants

WHRN p.Ser101Ala Uncertain significance ★ ⚠ same residue
WHRN p.Ser101= Likely benign ★ same residue
WHRN c.1203+2T>C Likely pathogenic ★★ same type
WHRN c.1417-1G>A Pathogenic/Likely pathogenic ★★ same type
WHRN p.Arg778Ter Pathogenic ★★ same type
WHRN p.Gln187Ter Pathogenic/Likely pathogenic ★★ same type
WHRN p.Trp374Ter Pathogenic/Likely pathogenic ★★ same type
WHRN c.*156G>A 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/whrn-p-ser101phe (accessed [today's date]).

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