Is CSAG1 p.Pro54Arg (c.161C>G) pathogenic?

CSAG1 p.Pro54Arg (c.161C>G) is classified Benign in CSAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-03). AlphaMissense: likely benign (0.1764); Low-frequency (popmax 3.99%, afr).

How common is CSAG1 p.Pro54Arg (c.161C>G) in the general population?

CSAG1 p.Pro54Arg (c.161C>G) is low-frequency (popmax 3.99%, afr) (gnomAD).

What do computational predictors say about CSAG1 p.Pro54Arg (c.161C>G)?

AlphaMissense predicts likely benign (score 0.1764) — an in-silico prediction, not a clinical call.

CSAG1 p.Pro54Arg

c.161C>G · rs1556830729 · VCV790250

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1764 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.99%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.1764	likely benign
SaProt	LLR -6.17	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 -0.48	GERP -0.73
Regional constraint	o/e 1.16	unconstrained · MANE · 4,663 bp · p 0.22 · regional, not allelic
Overall
CADD	13.64	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 3.99% African / African-American · 2,261/56,729 alleles

Filtering AF 3.85% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.79%

Overall 0.217% 2,620/1,208,796 alleles · low-frequency exomes 1,313/1,097,984 · genomes 1,307/110,812 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.99%	25
Remaining individualsnot grpmax-eligible	0.267%	375
Admixed American	0.256%	390
Middle Eastern	0.253%	395
European (non-Finnish)	0.0112%	8,949
South Asian	0.00706%	14,169

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.Pro54Arg
Coding: c.161C>G
MANE Select: NM_001102576
dbSNP: rs1556830729
Type: single nucleotide variant
Location: chrX:152728080 (GRCh38)
Structure: AlphaFold pLDDT 63.01
Residue 54: 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-pro54arg (accessed [today's date]).

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