Is SCAF4 p.Pro609= (c.1827T>C) pathogenic?

SCAF4 p.Pro609= (c.1827T>C) is classified Likely benign in SCAF4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-09). Very rare (popmax 0.00133%, afr); Associated with SCAF4-related disorder.

What condition is associated with SCAF4 p.Pro609= (c.1827T>C)?

SCAF4 p.Pro609= (c.1827T>C) is associated with SCAF4-related disorder (ClinVar).

How common is SCAF4 p.Pro609= (c.1827T>C) in the general population?

SCAF4 p.Pro609= (c.1827T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

SCAF4 p.Pro609=

c.1827T>C · VCV3351223

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, 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 -0.2	GERP -3.8, phastCons 0.001
Overall
CADD	7.034	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,928 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000868% 14/1,613,806 alleles · very rare exomes 13/1,461,584 · genomes 1/152,222 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,474
African / African-Americangrpmax	0.00133%	74,928
European (non-Finnish)	0.00102%	98,325

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro609=
Coding: c.1827T>C
MANE Select: NM_020706
Type: single nucleotide variant
Location: chr21:31690855 (GRCh38)
Gene constraint: LOEUF 0.285 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.53 · 1 PDB
Residue 609: 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.Pro609Leu Uncertain significance ★ ⚠ same residue
SCAF4 p.Pro609Ser Likely benign ★ 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

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-pro609 (accessed [today's date]).

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