Is CSGALNACT2 p.Arg500His (c.1499G>A) pathogenic?

CSGALNACT2 p.Arg500His (c.1499G>A) is classified Uncertain significance in CSGALNACT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely benign (0.177); Ultra-rare (popmax 0.0133%, amr).

How common is CSGALNACT2 p.Arg500His (c.1499G>A) in the general population?

CSGALNACT2 p.Arg500His (c.1499G>A) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about CSGALNACT2 p.Arg500His (c.1499G>A)?

AlphaMissense predicts likely benign (score 0.177) — an in-silico prediction, not a clinical call.

CSGALNACT2 p.Arg500His

c.1499G>A · rs144260871 · VCV2456136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.177 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.177	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -8.84	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 20 kb · p 7.2e-08 · regional, not allelic
Overall
CADD	29.7	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; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/60,014 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00347% 56/1,614,122 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,502
Finnishnot grpmax-eligible	0.00937%	10,670
East Asian	0.00669%	14,959
African / African-American	0.004%	25,007
South Asian	0.00329%	30,360
European (non-Finnish)	0.00271%	36,876
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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.Arg500His
Coding: c.1499G>A
MANE Select: NM_018590
dbSNP: rs144260871
Type: single nucleotide variant
Location: chr10:43183412 (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-arg500his (accessed [today's date]).

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