Is GHDC p.Glu306Gln (c.916G>C) pathogenic?

GHDC p.Glu306Gln (c.916G>C) is classified Uncertain significance in GHDC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-28). AlphaMissense: likely benign (0.0812); Very rare (popmax 0.00232%, amr).

How common is GHDC p.Glu306Gln (c.916G>C) in the general population?

GHDC p.Glu306Gln (c.916G>C) is very rare (popmax 0.00232%, amr) (gnomAD).

What do computational predictors say about GHDC p.Glu306Gln (c.916G>C)?

AlphaMissense predicts likely benign (score 0.0812) — an in-silico prediction, not a clinical call.

GHDC p.Glu306Gln

c.916G>C · VCV4671811

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0812 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00232%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0812	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -6.01	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 1.3	GERP 0.24, phastCons 0.76
Regional constraint	o/e 1.00	unconstrained · MANE · 2,780 bp · p 0.94 · regional, not allelic
Overall
CADD	14.77	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

Grpmax group 0.00232% Admixed American · 1/43,148 alleles

Overall 0.00013% 2/1,537,034 alleles · very rare exomes 2/1,384,660 · genomes 0/152,374 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00232%	43,148
European (non-Finnish)	8.73e-05%	1,145,450

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: GHDC
Protein: p.Glu306Gln
Coding: c.916G>C
MANE Select: NM_032484
Type: single nucleotide variant
Location: chr17:42191184 (GRCh38)
Gene constraint: LOEUF 1.127 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.77

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-glu306gln (accessed [today's date]).

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