Is SCARF2 p.Ser548Phe (c.1643C>T) pathogenic?

SCARF2 p.Ser548Phe (c.1643C>T) is classified Uncertain significance in SCARF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-26). AlphaMissense: likely pathogenic (0.9632); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with SCARF2 p.Ser548Phe (c.1643C>T)?

SCARF2 p.Ser548Phe (c.1643C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SCARF2 p.Ser548Phe (c.1643C>T) in the general population?

SCARF2 p.Ser548Phe (c.1643C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about SCARF2 p.Ser548Phe (c.1643C>T)?

AlphaMissense predicts likely pathogenic (score 0.9632) — an in-silico prediction, not a clinical call.

SCARF2 p.Ser548Phe

c.1643C>T · rs762904849 · VCV2319629

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9632 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9632	likely pathogenic
REVEL	0.238	benign-leaning
SaProt	LLR -8.83	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 3,952 bp · p 0.87 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S553F vs ClinVar S548F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,890 alleles

Overall 0.000124% 2/1,614,214 alleles · very rare exomes 2/1,461,852 · genomes 0/152,362 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,890
South Asian	0.0011%	91,074

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: SCARF2
Protein: p.Ser548Phe
Coding: c.1643C>T
MANE Select: NM_182895
dbSNP: rs762904849
Type: single nucleotide variant
Location: chr22:20427448 (GRCh38)
Gene constraint: LOEUF 0.992 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.63

Full SCARF2 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

SCARF2 p.Ala12Ser Uncertain significance ★★ ⚠ same condition
SCARF2 p.Ala627Val Uncertain significance ★★ ⚠ same condition
SCARF2 p.Ala854Thr Uncertain significance ★★ ⚠ same condition
SCARF2 p.Arg860Lys Uncertain significance ★★ ⚠ same condition
SCARF2 p.Asp378Glu Uncertain significance ★★ ⚠ same condition
SCARF2 p.Asp830Asn Uncertain significance ★★ ⚠ same condition
SCARF2 p.Glu581Gln Uncertain significance ★★ ⚠ same condition
SCARF2 p.Glu853Gly 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/scarf2-p-ser548phe (accessed [today's date]).

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