Is SH3PXD2B p.Pro110Arg (c.329C>G) pathogenic?

SH3PXD2B p.Pro110Arg (c.329C>G) is classified Uncertain significance in SH3PXD2B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.3057); Very rare (popmax 0.00306%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SH3PXD2B p.Pro110Arg (c.329C>G)?

SH3PXD2B p.Pro110Arg (c.329C>G) is associated with Inborn genetic diseases (ClinVar).

How common is SH3PXD2B p.Pro110Arg (c.329C>G) in the general population?

SH3PXD2B p.Pro110Arg (c.329C>G) is very rare (popmax 0.00306%, nfe) (gnomAD).

What do computational predictors say about SH3PXD2B p.Pro110Arg (c.329C>G)?

AlphaMissense predicts likely benign (score 0.3057) — an in-silico prediction, not a clinical call.

SH3PXD2B p.Pro110Arg

c.329C>G · rs776745582 · VCV1519345

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3057 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00306%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3057	likely benign
REVEL	0.245	benign-leaning
SaProt	LLR -10.19	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 115 kb · p 1e-08 · regional, not allelic
Overall
CADD	31.0	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 0.00306% European (non-Finnish) · 36/1,178,010 alleles

Filtering AF 0.00224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00199%

Overall 0.00242% 39/1,608,922 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00306%	32,723
African / African-American	0.00267%	37,427
South Asian	0.00111%	89,776

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: SH3PXD2B
Protein: p.Pro110Arg
Coding: c.329C>G
MANE Select: NM_001017995
dbSNP: rs776745582
Type: single nucleotide variant
Location: chr5:172382108 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.95
Residue 110: the px domain

Full SH3PXD2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SH3PXD2B p.Pro110His Uncertain significance ★ ⚠ same residue
SH3PXD2B p.Arg43Trp Likely pathogenic ★★ same condition
SH3PXD2B p.Ala431Val Uncertain significance ★★ ⚠ same condition
SH3PXD2B p.Arg244Lys Uncertain significance ★★ ⚠ same condition
SH3PXD2B p.Arg305Trp Uncertain significance ★★ ⚠ same condition
SH3PXD2B p.Arg539Gln Uncertain significance ★★ ⚠ same condition
SH3PXD2B p.Arg541Gln Uncertain significance ★★ ⚠ same condition
SH3PXD2B p.Arg541Trp Uncertain significance ★★ ⚠ same condition

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/sh3pxd2b-p-pro110arg (accessed [today's date]).

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