Is SLC35A2 p.Phe241= (c.723C>T) pathogenic?

SLC35A2 p.Phe241= (c.723C>T) is classified Likely benign in SLC35A2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-03-10). Very rare (popmax 0.00682%, nfe); Associated with SLC35A2-congenital disorder of glycosylation.

What condition is associated with SLC35A2 p.Phe241= (c.723C>T)?

SLC35A2 p.Phe241= (c.723C>T) is associated with SLC35A2-congenital disorder of glycosylation (ClinVar).

How common is SLC35A2 p.Phe241= (c.723C>T) in the general population?

SLC35A2 p.Phe241= (c.723C>T) is very rare (popmax 0.00682%, nfe) (gnomAD).

How is SLC35A2-CDG inherited?

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

SLC35A2 p.Phe241=

c.723C>T · rs781951327 · VCV1590785

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00682%, nfe)

Conditions

SLC35A2-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 -5.4	GERP -2.8
Overall
CADD	0.145	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00682% European (non-Finnish) · 61/894,433 alleles

Filtering AF 0.00541% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0049%

Overall 0.00529% 64/1,209,726 alleles · very rare exomes 64/1,095,749 · genomes 0/113,977 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00682%	14,663
African / African-American	0.00346%	28,932
Remaining individualsnot grpmax-eligible	0.0021%	47,531

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: SLC35A2
Protein: p.Phe241=
Coding: c.723C>T
MANE Select: NM_005660
dbSNP: rs781951327
Type: single nucleotide variant
Location: chrX:48905186 (GRCh38)
Structure: AlphaFold pLDDT 80.59
Residue 241: a UniProt-annotated variant site (in cdg2m); a UniProt-annotated variant site (in cdg2m; reduced udp-galactose transport in patient fibroblasts)

Full SLC35A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SLC35A2-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For SLC35A2-CDG (Orphanet):

Inheritance: Unknown
Onset: Infancy, Neonatal

Similar variants

SLC35A2 p.Gly282Arg Pathogenic ★★ same condition
SLC35A2 p.Met1Val Pathogenic/Likely pathogenic ★★ same condition
SLC35A2 p.Tyr267Cys Likely pathogenic ★★ same condition
SLC35A2 p.Val331Ile Pathogenic ★★ same condition
SLC35A2 p.Ala11Ser Uncertain significance ★★ ⚠ same condition
SLC35A2 p.Ala12Gly Uncertain significance ★★ ⚠ same condition
SLC35A2 p.Ala328Thr Uncertain significance ★★ ⚠ same condition
SLC35A2 p.Ala344Ser 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/slc35a2-p-phe241 (accessed [today's date]).

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