GEMIN4 p.Asp255=

Q: Is GEMIN4 p.Asp255= (c.765C>T) pathogenic?

GEMIN4 p.Asp255= (c.765C>T) is classified Benign in GEMIN4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-28). Common (popmax 18.9%, mid) — too common for a highly-penetrant pathogenic allele; Associated with neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities.

Q: What condition is associated with GEMIN4 p.Asp255= (c.765C>T)?

GEMIN4 p.Asp255= (c.765C>T) is associated with neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities (ClinVar).

Q: How common is GEMIN4 p.Asp255= (c.765C>T) in the general population?

GEMIN4 p.Asp255= (c.765C>T) is common (popmax 18.9%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.765C>T · rs35696687 · VCV1185311

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 18.9%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.066	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -9	GERP -4
Overall
CADD	0.322	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.9% Middle Eastern · 1,144/6,062 alleles

Filtering AF 18% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.6%

Overall 15.5% 249,961/1,613,600 alleles · common exomes 231,926/1,461,488 · genomes 18,035/152,112 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	19.3%	5
Ashkenazi Jewishnot grpmax-eligible	19.1%	5
Middle Easterngrpmax	18.9%	5
Amishnot grpmax-eligible	17.2%	6
European (non-Finnish)	17.2%	6
Remaining individualsnot grpmax-eligible	15.1%	7
South Asian	12.3%	8
Admixed American	8.13%	12
African / African-American	2.86%	35
East Asian	0.0624%	1,602

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: GEMIN4
Protein: p.Asp255=
Coding: c.765C>T
MANE Select: NM_015721
dbSNP: rs35696687
Type: single nucleotide variant
Location: chr17:747278 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.54

Full GEMIN4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with microcephaly, cataracts, and renal abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GEMIN4 p.Trp818Arg Pathogenic/Likely pathogenic ★★ same condition
GEMIN4 p.Ala186Val Uncertain significance ★★ ⚠ same condition
GEMIN4 p.Arg91Gln Uncertain significance ★★ ⚠ same condition
GEMIN4 p.Gln1032Ter Uncertain significance ★★ same condition
GEMIN4 p.Ser755Phe Uncertain significance ★★ ⚠ same condition
GEMIN4 c.10+80C>T Benign ★★ same condition
GEMIN4 p.Ala579Gly Benign ★★ same condition
GEMIN4 p.Arg1033Cys Benign ★★ same condition

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/gemin4-p-asp255 (accessed [today's date]).

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