Is CSGALNACT2 p.Ile403Val (c.1207A>G) pathogenic?

CSGALNACT2 p.Ile403Val (c.1207A>G) is classified Uncertain significance in CSGALNACT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.0828); Ultra-rare (popmax 0.0547%, afr).

How common is CSGALNACT2 p.Ile403Val (c.1207A>G) in the general population?

CSGALNACT2 p.Ile403Val (c.1207A>G) is ultra-rare (popmax 0.0547%, afr) (gnomAD).

What do computational predictors say about CSGALNACT2 p.Ile403Val (c.1207A>G)?

AlphaMissense predicts likely benign (score 0.0828) — an in-silico prediction, not a clinical call.

CSGALNACT2 p.Ile403Val

c.1207A>G · rs140002994 · VCV3078014

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0828 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0547%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0828	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -2.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.2	GERP 1.6, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 20 kb · p 7.2e-08 · regional, not allelic
Overall
CADD	19.94	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 0.0547% African / African-American · 41/74,928 alleles

Filtering AF 0.0414% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0368%

Overall 0.00285% 46/1,613,342 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0547%	1,828
Remaining individualsnot grpmax-eligible	0.0048%	20,815
Admixed American	0.00167%	59,996
European (non-Finnish)	8.48e-05%	1,179,473

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.Ile403Val
Coding: c.1207A>G
MANE Select: NM_018590
dbSNP: rs140002994
Type: single nucleotide variant
Location: chr10:43167051 (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-ile403val (accessed [today's date]).

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