Is GPC4 p.Phe143= (c.429C>T) pathogenic?

GPC4 p.Phe143= (c.429C>T) is classified Likely benign in GPC4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-09-04). Ultra-rare (popmax 0.0208%, eas); Associated with GPC4-related disorder.

What condition is associated with GPC4 p.Phe143= (c.429C>T)?

GPC4 p.Phe143= (c.429C>T) is associated with GPC4-related disorder (ClinVar).

How common is GPC4 p.Phe143= (c.429C>T) in the general population?

GPC4 p.Phe143= (c.429C>T) is ultra-rare (popmax 0.0208%, eas) (gnomAD).

GPC4 p.Phe143=

c.429C>T · VCV3350417

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0208%, eas)

Conditions

GPC4-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.27	GERP -1.2
Overall
CADD	8.616	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0208% East Asian · 7/33,706 alleles

Filtering AF 0.00969% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00691%

Overall 0.00207% 25/1,208,033 alleles · ultra-rare exomes 23/1,097,611 · genomes 2/110,422 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0208%	4,815
European (non-Finnish)	0.00201%	49,703

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: GPC4
Protein: p.Phe143=
Coding: c.429C>T
MANE Select: NM_001448
Type: single nucleotide variant
Location: chrX:133324427 (GRCh38)
Structure: AlphaFold pLDDT 83.68

Full GPC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GPC4-related disorder

Similar variants

GPC4 p.Gln537Ter Conflicting classifications of pathogenicity ★ same condition
GPC4 p.Ser490Asn Uncertain significance ★ ⚠ same condition
GPC4 p.Arg219Cys Uncertain significance ⚠ same condition
GPC4 c.878-7A>C Likely benign same condition
GPC4 p.Glu185= Likely benign same condition
GPC4 p.Leu13Gln Likely benign ⚠ same condition
GPC4 p.Gln506Ter Pathogenic ★★ same type
GPC4 p.Ala217Val 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/gpc4-p-phe143 (accessed [today's date]).

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