Is SCAF4 p.Val512= (c.1536G>T) pathogenic?

SCAF4 p.Val512= (c.1536G>T) is classified Likely benign in SCAF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-28). Very rare (popmax 0.00373%, nfe).

How common is SCAF4 p.Val512= (c.1536G>T) in the general population?

SCAF4 p.Val512= (c.1536G>T) is very rare (popmax 0.00373%, nfe) (gnomAD).

SCAF4 p.Val512=

c.1536G>T · VCV4946025

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00373%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.003	GERP -4.5, phastCons 0.78
Overall
CADD	7.551	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00373% European (non-Finnish) · 44/1,179,772 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00316% 51/1,613,718 alleles · very rare exomes 49/1,461,496 · genomes 2/152,222 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,621
Finnishnot grpmax-eligible	0.00469%	21,323
European (non-Finnish)grpmax	0.00373%	26,813

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.Val512=
Coding: c.1536G>T
MANE Select: NM_020706
Type: single nucleotide variant
Location: chr21:31692427 (GRCh38)
Gene constraint: LOEUF 0.285 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.53 · 1 PDB
Residue 512: the rrm domain; a UniProt-annotated variant site (in fzs; likely pathogenic)

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

Similar variants

SCAF4 p.Val512Ala Uncertain significance ★ ⚠ same residue
SCAF4 p.Arg447Ter Pathogenic ★★ same type
SCAF4 p.Arg475Ter Pathogenic ★★ same type
SCAF4 p.Arg477Ter Pathogenic ★★ same type
SCAF4 p.Arg491Ter Pathogenic/Likely pathogenic ★★ same type
SOD1 p.Gly73Ser Likely pathogenic ★★ same type
SCAF4 p.Arg71Gln Uncertain significance ★★ ⚠ same type
SCAF4 p.Asn627Ser Uncertain significance ★★ ⚠ 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/scaf4-p-val512 (accessed [today's date]).

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