Is RET p.Ser32Trp (c.95C>G) pathogenic?

RET p.Ser32Trp (c.95C>G) is classified Uncertain significance in RET (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-07). AlphaMissense: likely pathogenic (0.7054); Absent from gnomAD v4.1; Associated with RET-related disorder.

What condition is associated with RET p.Ser32Trp (c.95C>G)?

RET p.Ser32Trp (c.95C>G) is associated with RET-related disorder (ClinVar).

How common is RET p.Ser32Trp (c.95C>G) in the general population?

RET p.Ser32Trp (c.95C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RET p.Ser32Trp (c.95C>G)?

AlphaMissense predicts likely pathogenic (score 0.7054) — an in-silico prediction, not a clinical call.

RET p.Ser32Trp

c.95C>G · VCV3345040

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7054 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

RET-related disorder

Computational evidence

Protein change
AlphaMissense	0.7054	likely pathogenic
REVEL	0.573	indeterminate
SaProt	LLR -8.85	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 1,972 bp · p 4.9e-10 · regional, not allelic
Overall
CADD	27.1	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

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: RET
Protein: p.Ser32Trp
Coding: c.95C>G
MANE Select: NM_020975
Type: single nucleotide variant
Location: chr10:43100480 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 34 PDB
Residue 32: a β-strand; a UniProt-annotated variant site (in hscr1; familial form); the 'cadherin-like region 1 (cld1)' region

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

Disease context

RET-related disorder

Similar variants

RET p.Ser32Leu Likely pathogenic ★★ ⚠ same residue
RET p.Ser32= Conflicting classifications of pathogenicity ★ same residue
RET c.1759+1G>A Pathogenic/Likely pathogenic ★★ same condition
RET p.Arg180Ter Pathogenic ★★ same condition
RET p.Arg897Gln Pathogenic ★★ ⚠ same condition
RET p.Cys609Phe Pathogenic ★★ same condition
RET p.Cys609Tyr Pathogenic ★★ same condition
RET p.Cys611Arg Pathogenic/Likely pathogenic ★★ 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/ret-p-ser32trp (accessed [today's date]).

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