Is COG7 p.Phe324= (c.972C>T) pathogenic?

COG7 p.Phe324= (c.972C>T) is classified Likely benign in COG7 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-18). Ultra-rare (popmax 0.0267%, amr); Associated with COG7-congenital disorder of glycosylation.

What condition is associated with COG7 p.Phe324= (c.972C>T)?

COG7 p.Phe324= (c.972C>T) is associated with COG7-congenital disorder of glycosylation (ClinVar).

How common is COG7 p.Phe324= (c.972C>T) in the general population?

COG7 p.Phe324= (c.972C>T) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

How is COG7-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

COG7 p.Phe324=

c.972C>T · rs747262700 · VCV713009

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Conditions

COG7-congenital disorder of glycosylation

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 -0.89	GERP -2.8
Overall
CADD	6.824	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% Admixed American · 16/60,004 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00384% 62/1,614,134 alleles · ultra-rare exomes 50/1,461,884 · genomes 12/152,250 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,750
South Asian	0.00439%	22,773
European (non-Finnish)	0.00339%	29,501
East Asian	0.00223%	44,894
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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: COG7
Protein: p.Phe324=
Coding: c.972C>T
MANE Select: NM_153603
dbSNP: rs747262700
Type: single nucleotide variant
Location: chr16:23424786 (GRCh38)
Gene constraint: LOEUF 0.651 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.77

Full COG7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COG7-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For COG7-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

COG7 p.Phe324Leu Uncertain significance ★★ ⚠ same residue
COG7 c.318+1G>A Likely pathogenic ★★ same condition
COG7 p.Ala606Asp Pathogenic/Likely pathogenic ★★ ⚠ same condition
COG7 p.Arg444Ter Pathogenic/Likely pathogenic ★★ same condition
COG7 c.1475+4G>A Uncertain significance ★★ same condition
COG7 p.Ala194Val Uncertain significance ★★ ⚠ same condition
COG7 p.Ala222Thr Uncertain significance ★★ ⚠ same condition
COG7 p.Ala29Val 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/cog7-p-phe324 (accessed [today's date]).

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