Is SCAF4 p.Ser68Pro (c.202T>C) pathogenic?

SCAF4 p.Ser68Pro (c.202T>C) is classified Uncertain significance in SCAF4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-02-15). AlphaMissense: likely pathogenic (1); No allele count reported in gnomAD v4.1 (AN 1,595,174); Associated with Fliedner-Zweier syndrome.

What condition is associated with SCAF4 p.Ser68Pro (c.202T>C)?

SCAF4 p.Ser68Pro (c.202T>C) is associated with Fliedner-Zweier syndrome (ClinVar).

How common is SCAF4 p.Ser68Pro (c.202T>C) in the general population?

SCAF4 p.Ser68Pro (c.202T>C) is no allele count reported in gnomAD v4.1 (AN 1,595,174) (gnomAD).

What do computational predictors say about SCAF4 p.Ser68Pro (c.202T>C)?

AlphaMissense predicts likely pathogenic (score 1) — an in-silico prediction, not a clinical call.

SCAF4 p.Ser68Pro

c.202T>C · VCV4081883

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

1 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,595,174)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fliedner-Zweier syndrome

Computational evidence

Protein change
AlphaMissense	1	likely pathogenic · top 5% in SCAF4
REVEL	0.678	pathogenic-leaning
SaProt	LLR -12.87	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 29 kb · p 1.6e-12 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,595,174). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SCAF4
Protein: p.Ser68Pro
Coding: c.202T>C
MANE Select: NM_020706
Type: single nucleotide variant
Location: chr21:31703884 (GRCh38)
Gene constraint: LOEUF 0.285 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.53 · 1 PDB
Residue 68: the cid domain; an α-helix

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

Disease context

Fliedner-Zweier syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SCAF4 p.Arg447Ter Pathogenic ★★ same condition
SCAF4 p.Arg475Ter Pathogenic ★★ same condition
SCAF4 p.Arg477Ter Pathogenic ★★ same condition
SCAF4 p.Arg491Ter Pathogenic/Likely pathogenic ★★ same condition
SCAF4 c.160-1G>A Likely pathogenic ★ same condition
SCAF4 c.1885+2T>C Likely pathogenic ★ same condition
SCAF4 c.2209+1G>T Likely pathogenic ★ same condition
SCAF4 p.Arg471Ter Pathogenic ★ 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-ser68pro (accessed [today's date]).

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