Is SLC3A2 p.Pro415Ser (c.1243C>T) pathogenic?

SLC3A2 p.Pro415Ser (c.1243C>T) is classified Benign/Likely benign in SLC3A2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-18). AlphaMissense: likely benign (0.0846); Low-frequency (popmax 1.38%, afr).

How common is SLC3A2 p.Pro415Ser (c.1243C>T) in the general population?

SLC3A2 p.Pro415Ser (c.1243C>T) is low-frequency (popmax 1.38%, afr) (gnomAD).

What do computational predictors say about SLC3A2 p.Pro415Ser (c.1243C>T)?

AlphaMissense predicts likely benign (score 0.0846) — an in-silico prediction, not a clinical call.

SLC3A2 p.Pro415Ser

c.1243C>T · rs7944051 · VCV789487

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0846 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.38%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0846	likely benign
REVEL	0.242	benign-leaning
SaProt	LLR -7.22	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 -0.082	GERP -1.1
Regional constraint	o/e 0.83	unconstrained · MANE · 3,097 bp · p 0.013 · regional, not allelic
Overall
CADD	13.01	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P516S vs ClinVar P415S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.38% African / African-American · 1,037/75,036 alleles

Filtering AF 1.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.28%

Overall 0.0783% 1,264/1,613,958 alleles · low-frequency exomes 664/1,461,654 · genomes 600/152,304 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.38%	72
Middle Eastern	0.248%	404
Remaining individualsnot grpmax-eligible	0.13%	772
Admixed American	0.0983%	1,017
European (non-Finnish)	0.00576%	17,351
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,580
South Asian	0.0022%	45,539
Finnishnot grpmax-eligible	0.00156%	64,020

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: SLC3A2
Protein: p.Pro415Ser
Coding: c.1243C>T
MANE Select: NM_001013251
dbSNP: rs7944051
Type: single nucleotide variant
Location: chr11:62888346 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.01 · 44 PDB

Full SLC3A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SLC3A2 c.301+3G>A Benign ★★ same type
SLC3A2 p.Arg338Met Likely benign ★★ ⚠ same type
SLC3A2 p.Leu435= Benign ★★ same type
SLC3A2 p.Lys491Gln Benign ★★ same type
SLC3A2 p.Ala346Ser Uncertain significance ★ ⚠ same type
SLC3A2 p.Ala346Thr Uncertain significance ★ ⚠ same type
SLC3A2 p.Ala492Gly Uncertain significance ★ ⚠ same type
SLC3A2 p.Ala79Asp 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/slc3a2-p-pro415ser (accessed [today's date]).

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