Is GID4 p.Pro72Ser (c.214C>T) pathogenic?

GID4 p.Pro72Ser (c.214C>T) is classified Uncertain significance in GID4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-19). AlphaMissense: likely benign (0.0775); Ultra-rare (popmax 0.0765%, eas).

How common is GID4 p.Pro72Ser (c.214C>T) in the general population?

GID4 p.Pro72Ser (c.214C>T) is ultra-rare (popmax 0.0765%, eas) (gnomAD).

What do computational predictors say about GID4 p.Pro72Ser (c.214C>T)?

AlphaMissense predicts likely benign (score 0.0775) — an in-silico prediction, not a clinical call.

GID4 p.Pro72Ser

c.214C>T · rs533427067 · VCV2539694

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0775 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0765%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0775	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -8.57	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 5.4	GERP 1.3, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 376 bp · p 0.59 · regional, not allelic
Overall
CADD	21.0	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 0.0765% East Asian · 25/32,694 alleles

Filtering AF 0.0531% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0454%

Overall 0.00213% 30/1,409,118 alleles · ultra-rare exomes 21/1,257,420 · genomes 9/151,698 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0765%	1,308
Admixed American	0.00281%	35,622
Remaining individualsnot grpmax-eligible	0.00187%	53,532
European (non-Finnish)	0.000278%	360,120

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: GID4
Protein: p.Pro72Ser
Coding: c.214C>T
MANE Select: NM_024052
dbSNP: rs533427067
Type: single nucleotide variant
Location: chr17:18039678 (GRCh38)
Gene constraint: LOEUF 0.702 · pLI 0.75 (gnomAD)
Structure: AlphaFold pLDDT 76.05 · 31 PDB

Full GID4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GID4 p.Ala118Asp Uncertain significance ★ ⚠ same type
GID4 p.Ala38Glu Uncertain significance ★ ⚠ same type
GID4 p.Arg35Gly Uncertain significance ★ ⚠ same type
GID4 p.Arg49Leu Uncertain significance ★ ⚠ same type
GID4 p.Arg64Ser Uncertain significance ★ ⚠ same type
GID4 p.Asn285Ile Uncertain significance ★ ⚠ same type
GID4 p.Gln36Pro Uncertain significance ★ ⚠ same type
GID4 p.Glu224Lys 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/gid4-p-pro72ser (accessed [today's date]).

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