Is COG7 p.Pro701= (c.2103T>C) pathogenic?

COG7 p.Pro701= (c.2103T>C) is classified Benign in COG7 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 22.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with COG7-congenital disorder of glycosylation.

What condition is associated with COG7 p.Pro701= (c.2103T>C)?

COG7 p.Pro701= (c.2103T>C) is associated with COG7-congenital disorder of glycosylation (ClinVar).

How is COG7-CDG inherited?

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

COG7 p.Pro701=

Q: How common is COG7 p.Pro701= (c.2103T>C) in the general population?

COG7 p.Pro701= (c.2103T>C) is common (popmax 22.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2103T>C · rs8057712 · VCV96523

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 22.2%, afr) — too common for a highly-penetrant pathogenic allele

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 -14	GERP -3.4
Overall
CADD	0.035	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22.2% African / African-American · 16,642/74,980 alleles

Filtering AF 21.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 21.8%

Overall 4.08% 65,930/1,614,098 alleles · common exomes 52,331/1,461,888 · genomes 13,599/152,210 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	22.2%	5
Admixed American	9.6%	10
Middle Eastern	7.44%	13
Ashkenazi Jewishnot grpmax-eligible	7.17%	14
South Asian	5.38%	19
Remaining individualsnot grpmax-eligible	4.98%	20
Finnishnot grpmax-eligible	2.62%	38
European (non-Finnish)	2.57%	39
East Asian	2.09%	48
Amishnot grpmax-eligible	0.768%	130

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.Pro701=
Coding: c.2103T>C
MANE Select: NM_153603
dbSNP: rs8057712
Type: single nucleotide variant
Location: chr16:23392423 (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 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
COG7 p.Ala325Thr 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-pro701 (accessed [today's date]).

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