Is CSGALNACT2 p.Pro194Ser (c.580C>T) pathogenic?

CSGALNACT2 p.Pro194Ser (c.580C>T) is classified Uncertain significance in CSGALNACT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-24). AlphaMissense: likely benign (0.2008); Very rare (popmax 0.0011%, sas).

How common is CSGALNACT2 p.Pro194Ser (c.580C>T) in the general population?

CSGALNACT2 p.Pro194Ser (c.580C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CSGALNACT2 p.Pro194Ser (c.580C>T)?

AlphaMissense predicts likely benign (score 0.2008) — an in-silico prediction, not a clinical call.

CSGALNACT2 p.Pro194Ser

c.580C>T · rs752537770 · VCV2551644

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2008 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2008	likely benign
REVEL	0.205	benign-leaning
SaProt	LLR -14.46	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 8,753 bp · p 0.17 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,068 alleles

Overall 0.000658% 1/152,054 alleles · very rare

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: CSGALNACT2
Protein: p.Pro194Ser
Coding: c.580C>T
MANE Select: NM_018590
dbSNP: rs752537770
Type: single nucleotide variant
Location: chr10:43155729 (GRCh38)
Gene constraint: LOEUF 0.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.16

Full CSGALNACT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSGALNACT2 p.Ala186Val Uncertain significance ★ ⚠ same type
CSGALNACT2 p.Ala35Thr Uncertain significance ★ ⚠ same type
CSGALNACT2 p.Ala533Thr Uncertain significance ★ ⚠ same type
CSGALNACT2 p.Arg11Gln Uncertain significance ★ ⚠ same type
CSGALNACT2 p.Arg11Trp Uncertain significance ★ ⚠ same type
CSGALNACT2 p.Arg165Cys Uncertain significance ★ ⚠ same type
CSGALNACT2 p.Arg165His Uncertain significance ★ ⚠ same type
CSGALNACT2 p.Arg227Lys 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/csgalnact2-p-pro194ser (accessed [today's date]).

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