Is SH3D19 p.Pro677= (c.2031G>A) pathogenic?

SH3D19 p.Pro677= (c.2031G>A) is classified Likely benign in SH3D19 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-28). Ultra-rare (popmax 0.0267%, amr); Associated with SH3D19-related disorder.

What condition is associated with SH3D19 p.Pro677= (c.2031G>A)?

SH3D19 p.Pro677= (c.2031G>A) is associated with SH3D19-related disorder (ClinVar).

How common is SH3D19 p.Pro677= (c.2031G>A) in the general population?

SH3D19 p.Pro677= (c.2031G>A) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

SH3D19 p.Pro677=

c.2031G>A · rs370910406 · VCV3053221

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Conditions

SH3D19-related disorder

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 -1.5	GERP 0.63
Overall
CADD	11.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% Admixed American · 16/59,996 alleles

Filtering AF 0.0185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0177%

Overall 0.0177% 285/1,614,006 alleles · ultra-rare exomes 271/1,461,820 · genomes 14/152,186 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,750
European (non-Finnish)	0.0207%	4,836
East Asian	0.0178%	5,610
South Asian	0.00879%	11,383
African / African-American	0.00667%	15,000
Remaining individualsnot grpmax-eligible	0.0064%	15,626

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.Pro677=
Coding: c.2031G>A
MANE Select: NM_001378122
dbSNP: rs370910406
Type: single nucleotide variant
Location: chr4:151147973 (GRCh38)
Gene constraint: LOEUF 0.629 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.09
Residue 677: the sh3 4 domain

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

Disease context

SH3D19-related disorder

Similar variants

EBP p.Arg147His Pathogenic ★★ ⚠ same condition
EBP p.Gly161Arg Likely pathogenic ★★ same condition
EBP c.338+1G>A Pathogenic ★ same condition
EBP p.Gly161Glu Likely pathogenic ★ same condition
SH3D19 c.1534+9A>G Benign same condition
SH3D19 c.2083-245G>A Likely benign same condition
SH3D19 p.Arg646Gln Likely benign same condition
SH3D19 p.Arg695Cys Likely benign 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/sh3d19-p-pro677 (accessed [today's date]).

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