Is SLC9A2 p.Arg792Trp (c.2374C>T) pathogenic?

SLC9A2 p.Arg792Trp (c.2374C>T) is classified Uncertain significance in SLC9A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). AlphaMissense: likely benign (0.2904); Ultra-rare (popmax 0.06%, amr).

How common is SLC9A2 p.Arg792Trp (c.2374C>T) in the general population?

SLC9A2 p.Arg792Trp (c.2374C>T) is ultra-rare (popmax 0.06%, amr) (gnomAD).

What do computational predictors say about SLC9A2 p.Arg792Trp (c.2374C>T)?

AlphaMissense predicts likely benign (score 0.2904) — an in-silico prediction, not a clinical call.

SLC9A2 p.Arg792Trp

c.2374C>T · VCV4169264

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2904 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.06%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2904	likely benign
REVEL	0.298	indeterminate
SaProt	LLR -11.03	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5	GERP -1.7, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 3,831 bp · p 0.07 · regional, not allelic
Overall
CADD	24.1	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 0.06% Admixed American · 36/60,006 alleles

Filtering AF 0.0445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0392%

Overall 0.00273% 44/1,614,094 alleles · ultra-rare exomes 43/1,461,888 · genomes 1/152,206 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.06%	1,667
Remaining individualsnot grpmax-eligible	0.0032%	31,244
South Asian	0.0011%	91,092
European (non-Finnish)	0.000424%	236,009

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: SLC9A2
Protein: p.Arg792Trp
Coding: c.2374C>T
MANE Select: NM_003048
Type: single nucleotide variant
Location: chr2:102708424 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.40
Residue 792: the 'disordered' region

Full SLC9A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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SLC9A2 p.Ala39Thr Uncertain significance ★ ⚠ same type
SLC9A2 p.Ala406Val Uncertain significance ★ ⚠ same type
SLC9A2 p.Ala42Asp Uncertain significance ★ ⚠ same type
SLC9A2 p.Ala444Val Uncertain significance ★ ⚠ same type
SLC9A2 p.Ala497Thr Uncertain significance ★ ⚠ same type
SLC9A2 p.Ala53Val Uncertain significance ★ ⚠ same type
SLC9A2 p.Ala564Asp 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/slc9a2-p-arg792trp (accessed [today's date]).

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