Is SLC22A2 p.Ser313Phe (c.938C>T) pathogenic?

SLC22A2 p.Ser313Phe (c.938C>T) is classified Uncertain significance in SLC22A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-28). AlphaMissense: likely benign (0.1482); Very rare (popmax 0.00119%, nfe).

How common is SLC22A2 p.Ser313Phe (c.938C>T) in the general population?

SLC22A2 p.Ser313Phe (c.938C>T) is very rare (popmax 0.00119%, nfe) (gnomAD).

What do computational predictors say about SLC22A2 p.Ser313Phe (c.938C>T)?

AlphaMissense predicts likely benign (score 0.1482) — an in-silico prediction, not a clinical call.

SLC22A2 p.Ser313Phe

c.938C>T · VCV3319096

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1482 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1482	likely benign
REVEL	0.173	moderately benign-leaning
SaProt	LLR -9.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP -2.8, phastCons 0.99
Regional constraint	o/e 0.99	unconstrained · MANE · 41 kb · p 0.83 · regional, not allelic
Overall
CADD	18.77	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 0.00119% European (non-Finnish) · 14/1,174,480 alleles

Filtering AF 0.000692% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000541%

Overall 0.000871% 14/1,607,934 alleles · very rare exomes 13/1,455,768 · genomes 1/152,166 · 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: SLC22A2
Protein: p.Ser313Phe
Coding: c.938C>T
MANE Select: NM_003058
Type: single nucleotide variant
Location: chr6:160247203 (GRCh38)
Gene constraint: LOEUF 1.117 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.02 · 1 PDB

Full SLC22A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SLC22A2 p.Ala108Thr Uncertain significance ★ ⚠ same type
SLC22A2 p.Ala258Thr Uncertain significance ★ ⚠ same type
SLC22A2 p.Ala316Thr Uncertain significance ★ ⚠ same type
SLC22A2 p.Ala31Thr Uncertain significance ★ ⚠ same type
SLC22A2 p.Ala417Thr Uncertain significance ★ ⚠ same type
SLC22A2 p.Arg231Gln Uncertain significance ★ ⚠ same type
SLC22A2 p.Arg231Trp Uncertain significance ★ ⚠ same type
SLC22A2 p.Arg320Cys Uncertain significance ★ ⚠ 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/slc22a2-p-ser313phe (accessed [today's date]).

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