Is SLC18A2 p.Pro237= (c.711C>A) pathogenic?

SLC18A2 p.Pro237= (c.711C>A) is classified Likely benign in SLC18A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-15). Very rare (popmax 0.00932%, nfe).

How common is SLC18A2 p.Pro237= (c.711C>A) in the general population?

SLC18A2 p.Pro237= (c.711C>A) is very rare (popmax 0.00932%, nfe) (gnomAD).

SLC18A2 p.Pro237=

c.711C>A · rs769757368 · VCV1546171

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00932%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.012	GERP 1, phastCons 0.74
Overall
CADD	8.792	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00932% European (non-Finnish) · 110/1,180,040 alleles

Filtering AF 0.0079% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00735%

Overall 0.00706% 114/1,614,090 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00932%	10,728
Finnishnot grpmax-eligible	0.00468%	21,349
Remaining individualsnot grpmax-eligible	0.0016%	62,476

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: SLC18A2
Protein: p.Pro237=
Coding: c.711C>A
MANE Select: NM_003054
dbSNP: rs769757368
Type: single nucleotide variant
Location: chr10:117255287 (GRCh38)
Gene constraint: LOEUF 0.68 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.27 · 32 PDB
Residue 237: an α-helix; a disulfide bond

Full SLC18A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SLC18A2 p.Pro237Arg Uncertain significance ★ ⚠ same residue
SLC18A2 p.Pro237His Conflicting classifications of pathogenicity ★ ⚠ same residue
SLC18A2 p.Pro237Leu Uncertain significance ★ same residue
SLC18A2 p.Pro387Leu Pathogenic/Likely pathogenic ★★ same type
SLC18A2 c.834+6C>T Uncertain significance ★★ same type
SLC18A2 p.Ala164Val Uncertain significance ★★ ⚠ same type
SLC18A2 p.Ala425Val Uncertain significance ★★ ⚠ same type
SLC18A2 p.Arg17Cys 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/slc18a2-p-pro237 (accessed [today's date]).

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