Is GHDC p.Pro114Ser (c.340C>T) pathogenic?

GHDC p.Pro114Ser (c.340C>T) is classified Uncertain significance in GHDC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-30). AlphaMissense: likely benign (0.0724); Absent from gnomAD v4.1.

How common is GHDC p.Pro114Ser (c.340C>T) in the general population?

GHDC p.Pro114Ser (c.340C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GHDC p.Pro114Ser (c.340C>T)?

AlphaMissense predicts likely benign (score 0.0724) — an in-silico prediction, not a clinical call.

GHDC p.Pro114Ser

c.340C>T · VCV4029681

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0724 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0724	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -6.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -3.3, phastCons 0.001
Regional constraint	o/e 0.75	unconstrained · MANE · 1,094 bp · p 7.1e-05 · regional, not allelic
Overall
CADD	0.638	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: GHDC
Protein: p.Pro114Ser
Coding: c.340C>T
MANE Select: NM_032484
Type: single nucleotide variant
Location: chr17:42192953 (GRCh38)
Gene constraint: LOEUF 1.127 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.77
Residue 114: the 'disordered' region

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

Similar variants

GHDC p.Ala189Thr Uncertain significance ★ ⚠ same type
GHDC p.Ala223Val Uncertain significance ★ ⚠ same type
GHDC p.Ala225Gly Uncertain significance ★ ⚠ same type
GHDC p.Ala267Val Uncertain significance ★ ⚠ same type
GHDC p.Ala286Thr Uncertain significance ★ ⚠ same type
GHDC p.Ala291Thr Uncertain significance ★ ⚠ same type
GHDC p.Ala414Glu Uncertain significance ★ ⚠ same type
GHDC p.Ala436Thr 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/ghdc-p-pro114ser (accessed [today's date]).

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