Is CSGALNACT1 p.Pro167Arg (c.500C>G) pathogenic?

CSGALNACT1 p.Pro167Arg (c.500C>G) is classified Uncertain significance in CSGALNACT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-10). AlphaMissense: likely pathogenic (0.9729); Very rare (popmax 0.00667%, amr); Associated with Inborn genetic diseases.

What condition is associated with CSGALNACT1 p.Pro167Arg (c.500C>G)?

CSGALNACT1 p.Pro167Arg (c.500C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CSGALNACT1 p.Pro167Arg (c.500C>G) in the general population?

CSGALNACT1 p.Pro167Arg (c.500C>G) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about CSGALNACT1 p.Pro167Arg (c.500C>G)?

AlphaMissense predicts likely pathogenic (score 0.9729) — an in-silico prediction, not a clinical call.

CSGALNACT1 p.Pro167Arg

c.500C>G · VCV3497565

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9729 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9729	likely pathogenic · top 10% in CSGALNACT1
REVEL	0.572	indeterminate
SaProt	LLR -5.21	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 12	GERP 1.9, phastCons 1
Overall
CADD	29.2	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 0.00667% Admixed American · 4/59,996 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000372% 6/1,614,062 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,999
African / African-American	0.00267%	37,463

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: CSGALNACT1
Protein: p.Pro167Arg
Coding: c.500C>G
MANE Select: NM_001354483
Type: single nucleotide variant
Location: chr8:19505335 (GRCh38)
Gene constraint: LOEUF 1.257 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.71

Full CSGALNACT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CSGALNACT1 p.Pro167= Benign ★ same residue
CSGALNACT1 p.Ala195Ser Uncertain significance ★★ ⚠ same condition
CSGALNACT1 p.Ala259Gly Uncertain significance ★★ ⚠ same condition
CSGALNACT1 p.Ala401Ser Uncertain significance ★★ ⚠ same condition
CSGALNACT1 p.Ala48Gly Uncertain significance ★★ ⚠ same condition
CSGALNACT1 p.Arg202Cys Uncertain significance ★★ ⚠ same condition
CSGALNACT1 p.Arg202His Uncertain significance ★★ ⚠ same condition
CSGALNACT1 p.Arg238Gln Uncertain significance ★★ ⚠ same condition

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/csgalnact1-p-pro167arg (accessed [today's date]).

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