Is GPATCH11 p.Arg152Ter (c.454C>T) pathogenic?

GPATCH11 p.Arg152Ter (c.454C>T) is classified Pathogenic in GPATCH11 (ClinVar, No assertion criteria, 1 submitter). Very rare (popmax 0.00424%, amr); Associated with Early onset and severe retinal dystrophy with neurological impairment and facial dysmorphia.

How common is GPATCH11 p.Arg152Ter (c.454C>T) in the general population?

GPATCH11 p.Arg152Ter (c.454C>T) is very rare (popmax 0.00424%, amr) (gnomAD).

GPATCH11 p.Arg152Ter

Q: What condition is associated with GPATCH11 p.Arg152Ter (c.454C>T)?

GPATCH11 p.Arg152Ter (c.454C>T) is associated with Early onset and severe retinal dystrophy with neurological impairment and facial dysmorphia (ClinVar).

c.454C>T · rs574837250 · VCV3062156

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00424%, amr)

Conditions

Early onset and severe retinal dystrophy with neurological impairment and facial dysmorphia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 0.56, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00424% Admixed American · 2/47,196 alleles

Filtering AF 0.000703% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000263%

Overall 0.000518% 8/1,545,326 alleles · very rare exomes 6/1,393,714 · genomes 2/151,612 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00424%	23,598
African / African-American	0.00139%	71,802
South Asian	0.00127%	78,536
European (non-Finnish)	0.000348%	287,528

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: GPATCH11
Protein: p.Arg152Ter
Coding: c.454C>T
MANE Select: NM_174931
dbSNP: rs574837250
Type: single nucleotide variant
Location: chr2:37092169 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.60

Full GPATCH11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Early onset and severe retinal dystrophy with neurological impairment and facial dysmorphia

Similar variants

GPATCH11 p.Arg152Gln Uncertain significance ★ ⚠ same residue
GPATCH11 c.328+1G>T Pathogenic same condition
GPATCH11 c.449+1G>C Pathogenic same condition
GPATCH11 p.Tyr131Ter Pathogenic same condition
GPATCH11 p.Ala146Ser Uncertain significance ★ ⚠ same type
GPATCH11 p.Ala36Val Uncertain significance ★ ⚠ same type
GPATCH11 p.Ala46Val Uncertain significance ★ ⚠ same type
GPATCH11 p.Asn75Lys 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/gpatch11-p-arg152ter (accessed [today's date]).

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