Is SLC9B2 p.Pro415Ala (c.1243C>G) pathogenic?

SLC9B2 p.Pro415Ala (c.1243C>G) is classified Benign in SLC9B2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-30). AlphaMissense: likely benign (0.077); Low-frequency (popmax 3.26%, afr).

How common is SLC9B2 p.Pro415Ala (c.1243C>G) in the general population?

SLC9B2 p.Pro415Ala (c.1243C>G) is low-frequency (popmax 3.26%, afr) (gnomAD).

What do computational predictors say about SLC9B2 p.Pro415Ala (c.1243C>G)?

AlphaMissense predicts likely benign (score 0.077) — an in-silico prediction, not a clinical call.

SLC9B2 p.Pro415Ala

c.1243C>G · rs72943528 · VCV775219

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.077 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.26%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.077	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -7.54	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 2.3	GERP -1.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 41 kb · p 0.65 · regional, not allelic
Overall
CADD	18.88	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 3.26% African / African-American · 2,438/74,878 alleles

Filtering AF 3.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.1%

Overall 0.298% 4,798/1,611,908 alleles · low-frequency exomes 3,202/1,459,730 · genomes 1,596/152,178 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.26%	31
Middle Eastern	1.47%	68
Remaining individualsnot grpmax-eligible	0.393%	255
Admixed American	0.37%	270
South Asian	0.243%	411
European (non-Finnish)	0.13%	768
Ashkenazi Jewishnot grpmax-eligible	0.112%	895
East Asian	0.0357%	2,799
Finnishnot grpmax-eligible	0.00156%	63,974

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: SLC9B2
Protein: p.Pro415Ala
Coding: c.1243C>G
MANE Select: NM_178833
dbSNP: rs72943528
Type: single nucleotide variant
Location: chr4:103031712 (GRCh38)
Gene constraint: LOEUF 0.992 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.24 · 4 PDB
Residue 415: a turn

Full SLC9B2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SLC9B2 p.Thr379= Benign ★★ same type
SLC9B2 p.Val267= Benign ★★ same type
SLC9B2 p.Ala180Val Uncertain significance ★ ⚠ same type
SLC9B2 p.Ala350Thr Uncertain significance ★ ⚠ same type
SLC9B2 p.Ala392Val Uncertain significance ★ ⚠ same type
SLC9B2 p.Ala456Val Uncertain significance ★ ⚠ same type
SLC9B2 p.Arg330His Uncertain significance ★ ⚠ same type
SLC9B2 p.Arg339Ser 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/slc9b2-p-pro415ala (accessed [today's date]).

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