Is SCAF4 p.Pro687= (c.2061G>A) pathogenic?

SCAF4 p.Pro687= (c.2061G>A) is classified Likely benign in SCAF4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-03-14). Rare (popmax 0.133%, afr); Associated with SCAF4-related disorder.

What condition is associated with SCAF4 p.Pro687= (c.2061G>A)?

SCAF4 p.Pro687= (c.2061G>A) is associated with SCAF4-related disorder (ClinVar).

How common is SCAF4 p.Pro687= (c.2061G>A) in the general population?

SCAF4 p.Pro687= (c.2061G>A) is rare (popmax 0.133%, afr) (gnomAD).

SCAF4 p.Pro687=

c.2061G>A · VCV3358610

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.133%, afr)

Conditions

SCAF4-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 -14	GERP -4.5
Overall
CADD	0.152	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.133% African / African-American · 99/74,544 alleles

Filtering AF 0.112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.104%

Overall 0.0147% 236/1,601,696 alleles · rare exomes 167/1,449,504 · genomes 69/152,192 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.133%	753
Middle Eastern	0.0524%	1,909
Remaining individualsnot grpmax-eligible	0.0178%	5,622
European (non-Finnish)	0.00987%	10,129
Admixed American	0.0086%	11,634
Finnishnot grpmax-eligible	0.00316%	31,686

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: SCAF4
Protein: p.Pro687=
Coding: c.2061G>A
MANE Select: NM_020706
Type: single nucleotide variant
Location: chr21:31685716 (GRCh38)
Gene constraint: LOEUF 0.285 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.53 · 1 PDB
Residue 687: a UniProt-annotated variant site (in fzs; likely pathogenic)

Full SCAF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SCAF4-related disorder

Similar variants

SCAF4 p.Pro687Leu Uncertain significance ★ ⚠ same residue
SCAF4 c.959+1G>T Likely pathogenic ★ same condition
SCAF4 p.Gln191Ter Pathogenic ★ same condition
SCAF4 p.Gln76Glu Uncertain significance ★ ⚠ same condition
SCAF4 c.2209+1G>A Uncertain significance same condition
SCAF4 p.Ala3Val Uncertain significance ⚠ same condition
SCAF4 p.Gly1034Arg Uncertain significance ⚠ same condition
SCAF4 p.Pro609= 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/scaf4-p-pro687 (accessed [today's date]).

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