Is CSAG1 p.Ser52Pro (c.154T>C) pathogenic?

CSAG1 p.Ser52Pro (c.154T>C) is classified Likely benign in CSAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-11). AlphaMissense: likely benign (0.0458); Very rare (popmax 0.00353%, sas).

How common is CSAG1 p.Ser52Pro (c.154T>C) in the general population?

CSAG1 p.Ser52Pro (c.154T>C) is very rare (popmax 0.00353%, sas) (gnomAD).

What do computational predictors say about CSAG1 p.Ser52Pro (c.154T>C)?

AlphaMissense predicts likely benign (score 0.0458) — an in-silico prediction, not a clinical call.

CSAG1 p.Ser52Pro

c.154T>C · rs1556830738 · VCV2603660

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0458 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00353%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.0458	likely benign
SaProt	LLR -6.64	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.1	GERP -4.3
Regional constraint	o/e 1.16	unconstrained · MANE · 4,663 bp · p 0.22 · regional, not allelic
Overall
CADD	1.052	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 0.00353% South Asian · 2/56,660 alleles

Filtering AF 0.000585% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000219%

Overall 0.000662% 8/1,208,303 alleles · very rare exomes 7/1,097,985 · genomes 1/110,318 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00353%	28,330
East Asian	0.00297%	33,710
Finnishnot grpmax-eligible	0.00215%	46,411
European (non-Finnish)	0.000447%	223,686

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.Ser52Pro
Coding: c.154T>C
MANE Select: NM_001102576
dbSNP: rs1556830738
Type: single nucleotide variant
Location: chrX:152728087 (GRCh38)
Structure: AlphaFold pLDDT 63.01
Residue 52: 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-ser52pro (accessed [today's date]).

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