Is SCAF4 p.Pro404Ser (c.1210C>T) pathogenic?

SCAF4 p.Pro404Ser (c.1210C>T) is classified Uncertain significance in SCAF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.0631); Ultra-rare (popmax 0.012%, afr); Associated with Inborn genetic diseases.

What condition is associated with SCAF4 p.Pro404Ser (c.1210C>T)?

SCAF4 p.Pro404Ser (c.1210C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SCAF4 p.Pro404Ser (c.1210C>T) in the general population?

SCAF4 p.Pro404Ser (c.1210C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about SCAF4 p.Pro404Ser (c.1210C>T)?

AlphaMissense predicts likely benign (score 0.0631) — an in-silico prediction, not a clinical call.

SCAF4 p.Pro404Ser

c.1210C>T · VCV4160099

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0631 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0631	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -6.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.4, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 2,491 bp · p 0.073 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,944 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.000558% 9/1,614,062 alleles · ultra-rare exomes 4/1,461,836 · genomes 5/152,226 · joint denominator

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.Pro404Ser
Coding: c.1210C>T
MANE Select: NM_020706
Type: single nucleotide variant
Location: chr21:31694839 (GRCh38)
Gene constraint: LOEUF 0.285 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.53 · 1 PDB
Residue 404: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SCAF4 p.Arg71Gln Uncertain significance ★★ ⚠ same condition
SCAF4 p.Asn627Ser Uncertain significance ★★ ⚠ same condition
SCAF4 p.Lys635Glu Uncertain significance ★★ ⚠ same condition
SCAF4 p.Pro330Ala Uncertain significance ★★ ⚠ same condition
SCAF4 p.Ser139Gly Uncertain significance ★★ ⚠ same condition
SCAF4 p.Ser397Ala Uncertain significance ★★ ⚠ same condition
SCAF4 p.Val916Ile Uncertain significance ★★ ⚠ same condition
SCAF4 p.Ile575Val 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-pro404ser (accessed [today's date]).

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