Is CSAG1 p.Ser47Phe (c.140C>T) pathogenic?

CSAG1 p.Ser47Phe (c.140C>T) is classified Uncertain significance in CSAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: ambiguous (0.3688); Very rare (popmax 0.00593%, eas).

How common is CSAG1 p.Ser47Phe (c.140C>T) in the general population?

CSAG1 p.Ser47Phe (c.140C>T) is very rare (popmax 0.00593%, eas) (gnomAD).

What do computational predictors say about CSAG1 p.Ser47Phe (c.140C>T)?

AlphaMissense predicts ambiguous (score 0.3688) — an in-silico prediction, not a clinical call.

CSAG1 p.Ser47Phe

c.140C>T · rs1556830762 · VCV2542139

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3688 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00593%, eas)

Computational evidence

Protein change
AlphaMissense	0.3688	ambiguous
SaProt	LLR -7.60	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.1	GERP -5.9
Regional constraint	o/e 1.16	unconstrained · MANE · 4,663 bp · p 0.22 · regional, not allelic
Overall
CADD	4.836	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00593% East Asian · 2/33,742 alleles

Filtering AF 0.000982% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000367%

Overall 0.000165% 2/1,208,851 alleles · very rare exomes 1/1,097,960 · genomes 1/110,891 · 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: CSAG1
Protein: p.Ser47Phe
Coding: c.140C>T
MANE Select: NM_001102576
dbSNP: rs1556830762
Type: single nucleotide variant
Location: chrX:152728101 (GRCh38)
Structure: AlphaFold pLDDT 63.01
Residue 47: the 'disordered' region

Full CSAG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSAG1 p.Ala10Thr Uncertain significance ★ ⚠ same type
CSAG1 p.Ala17Thr Uncertain significance ★ ⚠ same type
CSAG1 p.Ala17Val Uncertain significance ★ ⚠ same type
CSAG1 p.Ala42Ser Uncertain significance ★ ⚠ same type
CSAG1 p.Arg18Gln Uncertain significance ★ ⚠ same type
CSAG1 p.Arg41Pro Uncertain significance ★ same type
CSAG1 p.Arg62Gly Uncertain significance ★ ⚠ same type
CSAG1 p.His50Leu 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/csag1-p-ser47phe (accessed [today's date]).

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