Is GPATCH4 p.Arg178Cys (c.532C>T) pathogenic?

GPATCH4 p.Arg178Cys (c.532C>T) is classified Uncertain significance in GPATCH4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). Very rare (popmax 0.00688%, afr).

How common is GPATCH4 p.Arg178Cys (c.532C>T) in the general population?

GPATCH4 p.Arg178Cys (c.532C>T) is very rare (popmax 0.00688%, afr) (gnomAD).

GPATCH4 p.Arg178Cys

c.532C>T · VCV3521502

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00688%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.382	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 2.5, phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00688% African / African-American · 5/72,668 alleles

Filtering AF 0.00348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00315%

Overall 0.00411% 64/1,557,116 alleles · very rare exomes 60/1,404,980 · genomes 4/152,136 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00688%	14,534
Remaining individualsnot grpmax-eligible	0.00665%	15,034
European (non-Finnish)	0.00448%	22,322
South Asian	0.00246%	40,617
East Asian	0.00224%	44,618

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: GPATCH4
Protein: p.Arg178Cys
Coding: c.532C>T
Type: single nucleotide variant
Location: chr1:156595809 (GRCh38)
Gene constraint: LOEUF 1.669 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.52

Full GPATCH4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GPATCH4 c.348+115G>A Uncertain significance ★ same type
GPATCH4 c.-65A>C Uncertain significance ★ same type
GPATCH4 c.-74G>C Uncertain significance ★ same type
GPATCH4 c.-79G>C Uncertain significance ★ same type
GPATCH4 p.Ala162Thr Uncertain significance ★ same type
GPATCH4 p.Ala174Pro Uncertain significance ★ same type
GPATCH4 p.Ala219Val Uncertain significance ★ same type
GPATCH4 p.Ala316Val 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/gpatch4-p-arg178cys (accessed [today's date]).

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