Is ALG3 p.Phe214= (c.642C>T) pathogenic?

ALG3 p.Phe214= (c.642C>T) is classified Likely benign in ALG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-09). Very rare (popmax 0.00801%, afr); Associated with ALG3-congenital disorder of glycosylation.

What condition is associated with ALG3 p.Phe214= (c.642C>T)?

ALG3 p.Phe214= (c.642C>T) is associated with ALG3-congenital disorder of glycosylation (ClinVar).

How common is ALG3 p.Phe214= (c.642C>T) in the general population?

ALG3 p.Phe214= (c.642C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

How is ALG3-CDG inherited?

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

ALG3 p.Phe214=

c.642C>T · rs545724911 · VCV735950

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Conditions

ALG3-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.034	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing
Pangolin	Δ0.28	loss · gain 0.03 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP -2.7	GERP -3.3
Overall
CADD	7.897	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,940 alleles

Filtering AF 0.00394% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00361%

Overall 0.00435% 70/1,610,436 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,490
Admixed American	0.00504%	19,843
European (non-Finnish)	0.00501%	19,975
Remaining individualsnot grpmax-eligible	0.00321%	31,191

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: ALG3
Protein: p.Phe214=
Coding: c.642C>T
MANE Select: NM_005787
dbSNP: rs545724911
Type: single nucleotide variant
Location: chr3:184244685 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.05

Full ALG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG3-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG3-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG3 c.444+1G>T Likely pathogenic ★★ same condition
ALG3 p.Arg171Gln Pathogenic/Likely pathogenic ★★ same condition
ALG3 p.Arg266Cys Pathogenic ★★ same condition
ALG3 p.Arg354Cys Likely pathogenic ★★ same condition
ALG3 p.Arg354His Pathogenic/Likely pathogenic ★★ same condition
ALG3 p.Asn174Ser Likely pathogenic ★★ ⚠ same condition
ALG3 p.Gly55= Pathogenic/Likely pathogenic ★★ same condition
ALG3 p.Ile69Thr 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/alg3-p-phe214 (accessed [today's date]).

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