Is COG4 p.Asp7= (c.21C>T) pathogenic?

COG4 p.Asp7= (c.21C>T) is classified Likely benign in COG4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-05-22). Very rare (popmax 0.00458%, nfe); Associated with COG4-related disorder.

What condition is associated with COG4 p.Asp7= (c.21C>T)?

COG4 p.Asp7= (c.21C>T) is associated with COG4-related disorder (ClinVar).

How common is COG4 p.Asp7= (c.21C>T) in the general population?

COG4 p.Asp7= (c.21C>T) is very rare (popmax 0.00458%, nfe) (gnomAD).

COG4 p.Asp7=

c.21C>T · rs762819793 · VCV3051981

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00458%, nfe)

Conditions

COG4-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -3.5
Overall
CADD	3.377	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00458% European (non-Finnish) · 54/1,180,044 alleles

Filtering AF 0.00358% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00321%

Overall 0.00353% 57/1,613,864 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00458%	21,853
Admixed American	0.00333%	29,993
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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: COG4
Protein: p.Asp7=
Coding: c.21C>T
MANE Select: NM_015386
dbSNP: rs762819793
Type: single nucleotide variant
Location: chr16:70523523 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.29 · 1 PDB
Residue 7: the 'disordered' region; the 'interaction with scfd1' region

Full COG4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COG4-related disorder

Similar variants

COG4 p.Arg177Ter Pathogenic/Likely pathogenic ★★ same condition
COG4 p.Arg468Gln Uncertain significance ★★ same condition
COG4 p.Gln311Ter Likely pathogenic ★ same condition
COG4 c.844+5G>C Uncertain significance ★ same condition
COG4 p.Asp778His Uncertain significance ★ same condition
COG4 p.Gly85Asp Uncertain significance ★ same condition
COG4 p.Thr680Pro Uncertain significance ★ same condition
COG4 p.Tyr50Phe Uncertain significance ★ 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/cog4-p-asp7 (accessed [today's date]).

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