Is SLC2A10 p.Phe40Ser (c.119T>C) pathogenic?

SLC2A10 p.Phe40Ser (c.119T>C) is classified Uncertain significance in SLC2A10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-31). AlphaMissense: ambiguous (0.4364); Very rare (popmax 0.00703%, nfe); Associated with arterial tortuosity syndrome.

What condition is associated with SLC2A10 p.Phe40Ser (c.119T>C)?

SLC2A10 p.Phe40Ser (c.119T>C) is associated with arterial tortuosity syndrome, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is SLC2A10 p.Phe40Ser (c.119T>C) in the general population?

SLC2A10 p.Phe40Ser (c.119T>C) is very rare (popmax 0.00703%, nfe) (gnomAD).

What do computational predictors say about SLC2A10 p.Phe40Ser (c.119T>C)?

AlphaMissense predicts ambiguous (score 0.4364) — an in-silico prediction, not a clinical call.

SLC2A10 p.Phe40Ser

c.119T>C · rs372166877 · VCV264055

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4364 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00703%, nfe)

Conditions

arterial tortuosity syndrome

Computational evidence

Protein change
AlphaMissense	0.4364	ambiguous
REVEL	0.46	indeterminate
SaProt	LLR -10.42	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP -0.51, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 24 kb · p 0.61 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00703% European (non-Finnish) · 83/1,180,034 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00533%

Overall 0.00539% 87/1,614,048 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00703%	14,217
Remaining individualsnot grpmax-eligible	0.0048%	20,828
Admixed American	0.00167%	60,008

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: SLC2A10
Protein: p.Phe40Ser
Coding: c.119T>C
MANE Select: NM_030777
dbSNP: rs372166877
Type: single nucleotide variant
Location: chr20:46725155 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.78

Full SLC2A10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

arterial tortuosity syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial thoracic aortic aneurysm and aortic dissection

Similar variants

SLC2A10 p.Phe40= Likely benign ★★ same residue
SLC2A10 c.1411+2T>A Pathogenic/Likely pathogenic ★★ same condition
SLC2A10 p.Arg105Cys Pathogenic/Likely pathogenic ★★ same condition
SLC2A10 p.Arg132Trp Pathogenic/Likely pathogenic ★★ same condition
SLC2A10 p.Arg229Ter Pathogenic ★★ same condition
SLC2A10 p.Arg231Gln Pathogenic ★★ same condition
SLC2A10 p.Arg231Trp Pathogenic/Likely pathogenic ★★ same condition
SLC2A10 p.Arg444Ter 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/slc2a10-p-phe40ser (accessed [today's date]).

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