Is SCFD1 p.Ser504Leu (c.1511C>T) pathogenic?

SCFD1 p.Ser504Leu (c.1511C>T) is classified Uncertain significance in SCFD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-11). AlphaMissense: likely benign (0.0926); Very rare (popmax 0.00223%, eas).

How common is SCFD1 p.Ser504Leu (c.1511C>T) in the general population?

SCFD1 p.Ser504Leu (c.1511C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about SCFD1 p.Ser504Leu (c.1511C>T)?

AlphaMissense predicts likely benign (score 0.0926) — an in-silico prediction, not a clinical call.

SCFD1 p.Ser504Leu

c.1511C>T · rs2502443697 · VCV2306347

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0926 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0926	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	LLR -9.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 113 kb · p 9.5e-06 · regional, not allelic
Overall
CADD	24.5	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 0.00223% East Asian · 1/44,858 alleles

Overall 0.000124% 2/1,613,708 alleles · very rare exomes 2/1,461,450 · genomes 0/152,258 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,858
European (non-Finnish)	8.48e-05%	1,179,760

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: SCFD1
Protein: p.Ser504Leu
Coding: c.1511C>T
MANE Select: NM_016106
dbSNP: rs2502443697
Type: single nucleotide variant
Location: chr14:30705843 (GRCh38)
Gene constraint: LOEUF 0.809 · pLI 0.23 (gnomAD)
Structure: AlphaFold pLDDT 85.70

Full SCFD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SCFD1 p.Ile70Thr Uncertain significance ★★ ⚠ same type
SCFD1 p.Ala134Val Uncertain significance ★ ⚠ same type
SCFD1 p.Ala206Asp Uncertain significance ★ ⚠ same type
SCFD1 p.Ala371Val Uncertain significance ★ ⚠ same type
SCFD1 p.Ala498Thr Uncertain significance ★ ⚠ same type
SCFD1 p.Ala503Thr Uncertain significance ★ ⚠ same type
SCFD1 p.Arg107Gln Uncertain significance ★ ⚠ same type
SCFD1 p.Arg357Gln 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/scfd1-p-ser504leu (accessed [today's date]).

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