Is SLC16A2 p.Pro486Ser (c.1456C>T) pathogenic?

SLC16A2 p.Pro486Ser (c.1456C>T) is classified Uncertain significance in SLC16A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-19). AlphaMissense: likely pathogenic (0.7321); Very rare (popmax 0.000112%, nfe).

How common is SLC16A2 p.Pro486Ser (c.1456C>T) in the general population?

SLC16A2 p.Pro486Ser (c.1456C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about SLC16A2 p.Pro486Ser (c.1456C>T)?

AlphaMissense predicts likely pathogenic (score 0.7321) — an in-silico prediction, not a clinical call.

SLC16A2 p.Pro486Ser

c.1456C>T · rs2147350833 · VCV1313903

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7321 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7321	likely pathogenic
REVEL	0.453	indeterminate
SaProt	LLR -8.71	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 6,945 bp · p 3.2e-07 · regional, not allelic
Overall
CADD	25.6	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 0.000112% European (non-Finnish) · 1/894,788 alleles

Overall 8.26e-05% 1/1,211,165 alleles · very rare exomes 1/1,097,362 · genomes 0/113,803 · joint denominator

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: SLC16A2
Protein: p.Pro486Ser
Coding: c.1456C>T
MANE Select: NM_006517
dbSNP: rs2147350833
Type: single nucleotide variant
Location: chrX:74531389 (GRCh38)
Structure: AlphaFold pLDDT 79.48 · 7 PDB
Residue 486: an α-helix

Full SLC16A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SLC16A2 c.1399+1G>A Pathogenic ★★ same type
SLC16A2 c.576-1G>A Pathogenic/Likely pathogenic ★★ same type
SLC16A2 p.Ala150Val Pathogenic/Likely pathogenic ★★ ⚠ same type
SLC16A2 p.Arg171Ter Pathogenic ★★ same type
SLC16A2 p.Arg314Ter Pathogenic ★★ same type
SLC16A2 p.Arg371Cys Pathogenic/Likely pathogenic ★★ same type
SLC16A2 p.Asp424Asn Likely pathogenic ★★ ⚠ same type
SLC16A2 p.Gln16Ter Pathogenic ★★ same type

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/slc16a2-p-pro486ser (accessed [today's date]).

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