Is SLC5A6 p.Ile150Val (c.448A>G) pathogenic?

SLC5A6 p.Ile150Val (c.448A>G) is classified Likely benign in SLC5A6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-26). AlphaMissense: likely benign (0.1401); Ultra-rare (popmax 0.02%, eas); Associated with Inborn genetic diseases.

What condition is associated with SLC5A6 p.Ile150Val (c.448A>G)?

SLC5A6 p.Ile150Val (c.448A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SLC5A6 p.Ile150Val (c.448A>G) in the general population?

SLC5A6 p.Ile150Val (c.448A>G) is ultra-rare (popmax 0.02%, eas) (gnomAD).

What do computational predictors say about SLC5A6 p.Ile150Val (c.448A>G)?

AlphaMissense predicts likely benign (score 0.1401) — an in-silico prediction, not a clinical call.

SLC5A6 p.Ile150Val

c.448A>G · VCV3444902

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1401 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1401	likely benign
REVEL	0.53	indeterminate
SaProt	LLR -7.70	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.5	GERP 2.5, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 7,211 bp · p 9.5e-07 · regional, not allelic
Overall
CADD	20.5	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 0.02% East Asian · 9/44,892 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.000744% 12/1,613,208 alleles · ultra-rare exomes 9/1,461,030 · genomes 3/152,178 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.02%	4,988
Remaining individualsnot grpmax-eligible	0.0032%	31,232
South Asian	0.0011%	91,078

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: SLC5A6
Protein: p.Ile150Val
Coding: c.448A>G
MANE Select: NM_021095
Type: single nucleotide variant
Location: chr2:27206888 (GRCh38)
Gene constraint: LOEUF 0.609 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 79.99 · 5 PDB
Residue 150: a UniProt-annotated variant site (in smvtd and comnb; reduced membrane localization; impaired biotin transport)

Full SLC5A6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SLC5A6 p.Arg285Cys Uncertain significance ★★ ⚠ same condition
SLC5A6 p.Arg53Gln Uncertain significance ★★ ⚠ same condition
SLC5A6 p.Val189Ile Likely benign ★★ same condition
SLC5A6 p.Ala192Val Uncertain significance ★ ⚠ same condition
SLC5A6 p.Ala317Val Uncertain significance ★ ⚠ same condition
SLC5A6 p.Ala357Val Uncertain significance ★ ⚠ same condition
SLC5A6 p.Ala41Gly Uncertain significance ★ ⚠ same condition
SLC5A6 p.Arg240Cys 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/slc5a6-p-ile150val (accessed [today's date]).

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