Is CSGALNACT2 p.Ala186Val (c.557C>T) pathogenic?

CSGALNACT2 p.Ala186Val (c.557C>T) is classified Uncertain significance in CSGALNACT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-10). AlphaMissense: likely benign (0.2253); Ultra-rare (popmax 0.0106%, nfe).

How common is CSGALNACT2 p.Ala186Val (c.557C>T) in the general population?

CSGALNACT2 p.Ala186Val (c.557C>T) is ultra-rare (popmax 0.0106%, nfe) (gnomAD).

What do computational predictors say about CSGALNACT2 p.Ala186Val (c.557C>T)?

AlphaMissense predicts likely benign (score 0.2253) — an in-silico prediction, not a clinical call.

CSGALNACT2 p.Ala186Val

c.557C>T · rs760121385 · VCV2235958

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2253 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0106%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2253	likely benign
REVEL	0.244	benign-leaning
SaProt	LLR -7.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 8,753 bp · p 0.17 · regional, not allelic
Overall
CADD	25.9	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 0.0106% European (non-Finnish) · 125/1,180,004 alleles

Filtering AF 0.00906% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00844%

Overall 0.0088% 142/1,613,956 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0106%	9,440
African / African-American	0.00935%	10,701
Remaining individualsnot grpmax-eligible	0.0064%	15,621
Finnishnot grpmax-eligible	0.00469%	21,332
East Asian	0.00445%	22,448
South Asian	0.0011%	91,078

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.Ala186Val
Coding: c.557C>T
MANE Select: NM_018590
dbSNP: rs760121385
Type: single nucleotide variant
Location: chr10:43155706 (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.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
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-ala186val (accessed [today's date]).

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