Is CSAG1 p.Pro67Leu (c.200C>T) pathogenic?

CSAG1 p.Pro67Leu (c.200C>T) is classified Uncertain significance in CSAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-17). AlphaMissense: likely benign (0.154); Ultra-rare (popmax 0.0458%, mid).

How common is CSAG1 p.Pro67Leu (c.200C>T) in the general population?

CSAG1 p.Pro67Leu (c.200C>T) is ultra-rare (popmax 0.0458%, mid) (gnomAD).

What do computational predictors say about CSAG1 p.Pro67Leu (c.200C>T)?

AlphaMissense predicts likely benign (score 0.154) — an in-silico prediction, not a clinical call.

CSAG1 p.Pro67Leu

c.200C>T · rs1556830577 · VCV2392908

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.154 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0458%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.154	likely benign
SaProt	LLR -6.36	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 -9.3	GERP -4.6
Regional constraint	o/e 1.16	unconstrained · MANE · 4,663 bp · p 0.22 · regional, not allelic
Overall
CADD	14.0	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; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0458% Middle Eastern · 2/4,368 alleles

Filtering AF 0.00814% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00756%

Overall 0.0091% 110/1,209,150 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0458%	2,184
Finnishnot grpmax-eligible	0.015%	6,658
Remaining individualsnot grpmax-eligible	0.0126%	7,928
South Asian	0.0106%	9,454
European (non-Finnish)	0.00984%	10,167
Admixed American	0.00219%	45,728

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.Pro67Leu
Coding: c.200C>T
MANE Select: NM_001102576
dbSNP: rs1556830577
Type: single nucleotide variant
Location: chrX:152727831 (GRCh38)
Structure: AlphaFold pLDDT 63.01
Residue 67: 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-pro67leu (accessed [today's date]).

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