Is COG4 p.Ser383Phe (c.1148C>T) pathogenic?

COG4 p.Ser383Phe (c.1148C>T) is classified Uncertain significance in COG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-21). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with COG4 p.Ser383Phe (c.1148C>T)?

COG4 p.Ser383Phe (c.1148C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COG4 p.Ser383Phe (c.1148C>T) in the general population?

COG4 p.Ser383Phe (c.1148C>T) is absent from gnomAD v4.1 (gnomAD).

COG4 p.Ser383Phe

c.1148C>T · rs2507511520 · VCV3147105

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.25	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 43 kb · p 0.075 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COG4
Protein: p.Ser383Phe
Coding: c.1148C>T
MANE Select: NM_015386
dbSNP: rs2507511520
Type: single nucleotide variant
Location: chr16:70501005 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.29 · 1 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COG4 p.Ala251Thr Uncertain significance ★★ same condition
COG4 p.Ala544Val Uncertain significance ★★ same condition
COG4 p.Ala599Thr Uncertain significance ★★ same condition
COG4 p.Arg177Gln Uncertain significance ★★ same condition
COG4 p.Arg198His Uncertain significance ★★ same condition
COG4 p.Arg266Gln Uncertain significance ★★ same condition
COG4 p.Arg702Gln Uncertain significance ★★ same condition
COG4 p.Arg763His 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-ser383phe (accessed [today's date]).

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