Is SLC16A6 p.Ile431Met (c.1293A>G) pathogenic?

SLC16A6 p.Ile431Met (c.1293A>G) is classified Uncertain significance in SLC16A6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely benign (0.0811); Ultra-rare (popmax 0.064%, afr).

How common is SLC16A6 p.Ile431Met (c.1293A>G) in the general population?

SLC16A6 p.Ile431Met (c.1293A>G) is ultra-rare (popmax 0.064%, afr) (gnomAD).

What do computational predictors say about SLC16A6 p.Ile431Met (c.1293A>G)?

AlphaMissense predicts likely benign (score 0.0811) — an in-silico prediction, not a clinical call.

SLC16A6 p.Ile431Met

c.1293A>G · VCV3442803

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0811 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.064%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0811	likely benign
REVEL	0.246	benign-leaning
SaProt	LLR -9.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.7	GERP -2.9
Regional constraint	o/e 0.31	constrained · MANE · 1,841 bp · p 1.4e-17 · regional, not allelic
Overall
CADD	14.55	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.064% African / African-American · 48/75,034 alleles

Filtering AF 0.0495% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0444%

Overall 0.00366% 59/1,613,980 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.064%	1,563
Admixed American	0.01%	10,003
Remaining individualsnot grpmax-eligible	0.0064%	15,623
European (non-Finnish)	8.48e-05%	1,179,924

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: SLC16A6
Protein: p.Ile431Met
Coding: c.1293A>G
MANE Select: NM_001267727 · reported on NM_004694
Type: single nucleotide variant
Location: chr17:68270867 (GRCh38)

Full SLC16A6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/slc16a6-p-ile431met (accessed [today's date]).

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