Is SH3D19 p.Arg950Pro (c.2849G>C) pathogenic?

SH3D19 p.Arg950Pro (c.2849G>C) is classified Uncertain significance in SH3D19 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-26). AlphaMissense: likely benign (0.3359); Very rare (popmax 0.00169%, nfe).

How common is SH3D19 p.Arg950Pro (c.2849G>C) in the general population?

SH3D19 p.Arg950Pro (c.2849G>C) is very rare (popmax 0.00169%, nfe) (gnomAD).

What do computational predictors say about SH3D19 p.Arg950Pro (c.2849G>C)?

AlphaMissense predicts likely benign (score 0.3359) — an in-silico prediction, not a clinical call.

SH3D19 p.Arg950Pro

c.2849G>C · VCV3318067

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3359 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00169%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3359	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -10.72	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 -4.9	GERP -1.2
Regional constraint	o/e 0.86	unconstrained · MANE · 203 kb · p 1.1e-06 · regional, not allelic
Overall
CADD	17.41	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 R693P vs ClinVar R950P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00169% European (non-Finnish) · 20/1,179,982 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.0013% 21/1,613,992 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00169%	58,999
Admixed American	0.00167%	59,996

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: SH3D19
Protein: p.Arg950Pro
Coding: c.2849G>C
MANE Select: NM_001378122
Type: single nucleotide variant
Location: chr4:151128250 (GRCh38)
Gene constraint: LOEUF 0.629 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.09

Full SH3D19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EBP p.Arg110Gln Pathogenic/Likely pathogenic ★★ same type
EBP p.Arg110Ter Pathogenic ★★ same type
EBP p.Arg147Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
EBP p.Arg147His Pathogenic ★★ ⚠ same type
EBP p.Arg62Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
EBP p.Glu80Lys Pathogenic/Likely pathogenic ★★ same type
EBP p.Gly161Arg Likely pathogenic ★★ same type
EBP p.Ser98Phe Pathogenic/Likely pathogenic ★★ ⚠ 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/sh3d19-p-arg950pro (accessed [today's date]).

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