Is CSGALNACT2 p.Arg165His (c.494G>A) pathogenic?

CSGALNACT2 p.Arg165His (c.494G>A) is classified Uncertain significance in CSGALNACT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-16). AlphaMissense: likely pathogenic (0.5763); Ultra-rare (popmax 0.017%, nfe).

How common is CSGALNACT2 p.Arg165His (c.494G>A) in the general population?

CSGALNACT2 p.Arg165His (c.494G>A) is ultra-rare (popmax 0.017%, nfe) (gnomAD).

What do computational predictors say about CSGALNACT2 p.Arg165His (c.494G>A)?

AlphaMissense predicts likely pathogenic (score 0.5763) — an in-silico prediction, not a clinical call.

CSGALNACT2 p.Arg165His

c.494G>A · rs201853037 · VCV2362747

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5763 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5763	likely pathogenic
REVEL	0.347	indeterminate
SaProt	LLR -5.43	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 8,753 bp · p 0.17 · regional, not allelic
Overall
CADD	32.0	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 0.017% European (non-Finnish) · 201/1,180,022 alleles

Filtering AF 0.0151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0143%

Overall 0.0129% 209/1,613,988 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.017%	5,871
Remaining individualsnot grpmax-eligible	0.0048%	20,829
African / African-American	0.00401%	24,962
Admixed American	0.00167%	59,998
Finnishnot grpmax-eligible	0.00156%	64,012

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.Arg165His
Coding: c.494G>A
MANE Select: NM_018590
dbSNP: rs201853037
Type: single nucleotide variant
Location: chr10:43155643 (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.Arg165Cys Uncertain significance ★ ⚠ same residue
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.Arg227Lys Uncertain significance ★ ⚠ same type
CSGALNACT2 p.Arg252His 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-arg165his (accessed [today's date]).

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