Is CSGALNACT1 p.Pro392Ser (c.1174C>T) pathogenic?

CSGALNACT1 p.Pro392Ser (c.1174C>T) is classified Uncertain significance in CSGALNACT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-24). AlphaMissense: likely pathogenic (0.6538); Very rare (popmax 0.00167%, amr).

How common is CSGALNACT1 p.Pro392Ser (c.1174C>T) in the general population?

CSGALNACT1 p.Pro392Ser (c.1174C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CSGALNACT1 p.Pro392Ser (c.1174C>T)?

AlphaMissense predicts likely pathogenic (score 0.6538) — an in-silico prediction, not a clinical call.

CSGALNACT1 p.Pro392Ser

c.1174C>T · rs756351855 · VCV1430111

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6538 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6538	likely pathogenic
REVEL	0.656	pathogenic-leaning
SaProt	LLR -11.54	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00167% Admixed American · 1/60,020 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000274% 4/1,461,384 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,020
European (non-Finnish)	0.000254%	393,185

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.Pro392Ser
Coding: c.1174C>T
MANE Select: NM_001354483
dbSNP: rs756351855
Type: single nucleotide variant
Location: chr8:19418709 (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

Similar variants

CSGALNACT1 p.Asn264Ser Likely pathogenic ★★ ⚠ same type
CSGALNACT1 c.634+5G>C Uncertain significance ★★ same type
CSGALNACT1 p.Ala195Ser Uncertain significance ★★ ⚠ same type
CSGALNACT1 p.Ala259Gly Uncertain significance ★★ ⚠ same type
CSGALNACT1 p.Ala401Ser Uncertain significance ★★ ⚠ same type
CSGALNACT1 p.Ala48Gly Uncertain significance ★★ ⚠ same type
CSGALNACT1 p.Arg202Cys Uncertain significance ★★ ⚠ same type
CSGALNACT1 p.Arg202His 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/csgalnact1-p-pro392ser (accessed [today's date]).

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