Is GCDH p.Pro151Ser (c.451C>T) pathogenic?

GCDH p.Pro151Ser (c.451C>T) is classified Uncertain significance in GCDH (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-09-16). AlphaMissense: likely benign (0.2414); Very rare (popmax 0.000124%).

How common is GCDH p.Pro151Ser (c.451C>T) in the general population?

GCDH p.Pro151Ser (c.451C>T) is very rare (popmax 0.000124%) (gnomAD).

What do computational predictors say about GCDH p.Pro151Ser (c.451C>T)?

AlphaMissense predicts likely benign (score 0.2414) — an in-silico prediction, not a clinical call.

GCDH p.Pro151Ser

c.451C>T · rs1223762032 · VCV591699

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2414 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000124%)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2414	likely benign
REVEL	0.883	moderately pathogenic-leaning
SaProt	LLR -10.51	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.3	GERP 0.45, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 8,233 bp · p 0.00042 · regional, not allelic
Overall
CADD	23.6	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 0.000124%

Overall 0.000124% 2/1,614,084 alleles · very rare exomes 2/1,461,834 · genomes 0/152,250 · 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: GCDH
Protein: p.Pro151Ser
Coding: c.451C>T
MANE Select: NM_000159
dbSNP: rs1223762032
Type: single nucleotide variant
Location: chr19:12893599 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.23 · 4 PDB
Residue 151: an α-helix

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

Similar variants

GCDH c.1082+2T>C Pathogenic/Likely pathogenic ★★ same type
GCDH c.1243+1G>T Pathogenic ★★ same type
GCDH c.1244-2A>C Pathogenic ★★ same type
GCDH c.127+1G>A Pathogenic ★★ same type
GCDH c.127+1G>T Pathogenic/Likely pathogenic ★★ same type
GCDH c.271+1G>A Pathogenic ★★ same type
GCDH c.334+1G>A Likely pathogenic ★★ same type
GCDH c.505+1G>A Pathogenic ★★ 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/gcdh-p-pro151ser (accessed [today's date]).

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