Is COG5 p.Ile151Val (c.451A>G) pathogenic?

COG5 p.Ile151Val (c.451A>G) is classified Benign/Likely benign in COG5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.1801); Low-frequency (popmax 2.14%, eas); Associated with COG5-congenital disorder of glycosylation.

What condition is associated with COG5 p.Ile151Val (c.451A>G)?

COG5 p.Ile151Val (c.451A>G) is associated with COG5-congenital disorder of glycosylation (ClinVar).

How common is COG5 p.Ile151Val (c.451A>G) in the general population?

COG5 p.Ile151Val (c.451A>G) is low-frequency (popmax 2.14%, eas) (gnomAD).

How is COG5-CDG inherited?

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

What do computational predictors say about COG5 p.Ile151Val (c.451A>G)?

AlphaMissense predicts likely benign (score 0.1801) — an in-silico prediction, not a clinical call.

COG5 p.Ile151Val

c.451A>G · rs79413133 · VCV358472

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1801 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.14%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

COG5-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.1801	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -8.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 360 kb · p 0.0042 · regional, not allelic
Overall
CADD	19.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I182V vs ClinVar I151V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.14% East Asian · 960/44,836 alleles

Filtering AF 2.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.98%

Overall 0.085% 1,371/1,613,522 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	2.14%	47
Ashkenazi Jewishnot grpmax-eligible	0.524%	191
Remaining individualsnot grpmax-eligible	0.224%	446
South Asian	0.0681%	1,468
Admixed American	0.0167%	5,998
African / African-American	0.012%	8,332
European (non-Finnish)	0.00288%	34,700
Finnishnot grpmax-eligible	0.00157%	63,878

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: COG5
Protein: p.Ile151Val
Coding: c.451A>G
MANE Select: NM_006348
dbSNP: rs79413133
Type: single nucleotide variant
Location: chr7:107527324 (GRCh38)
Gene constraint: LOEUF 1.026 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.37

Full COG5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COG5-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For COG5-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

COG5 p.Ile151Lys Uncertain significance ★ same residue
COG5 c.1475+1G>A Likely pathogenic ★★ same condition
COG5 c.2295+2T>C Pathogenic/Likely pathogenic ★★ same condition
COG5 p.Arg205Ter Pathogenic ★★ same condition
COG5 p.Arg283Ter Pathogenic ★★ same condition
COG5 p.Arg461Ter Pathogenic/Likely pathogenic ★★ same condition
COG5 p.Arg690Ter Pathogenic/Likely pathogenic ★★ same condition
COG5 p.Arg708Ter Pathogenic/Likely pathogenic ★★ 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/cog5-p-ile151val (accessed [today's date]).

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