Is CDSN p.Ala368= (c.1104A>G) pathogenic?

CDSN p.Ala368= (c.1104A>G) is classified Benign in CDSN (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-04). Common (popmax 68.5%, eas) — too common for a highly-penetrant pathogenic allele.

CDSN p.Ala368=

Q: How common is CDSN p.Ala368= (c.1104A>G) in the general population?

CDSN p.Ala368= (c.1104A>G) is common (popmax 68.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1104A>G · rs1042126 · VCV1601246

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 68.5%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.38
Overall
CADD	4.809	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 68.5% East Asian · 30,652/44,746 alleles

Filtering AF 67.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 67.6%

Overall 51.6% 830,661/1,610,486 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	68.5%	1
African / African-American	67.9%	1
Middle Eastern	67.9%	1
Ashkenazi Jewishnot grpmax-eligible	65.9%	2
South Asian	63.4%	2
Admixed American	59.8%	2
Remaining individualsnot grpmax-eligible	52.8%	2
Finnishnot grpmax-eligible	50.8%	2
European (non-Finnish)	48.1%	2
Amishnot grpmax-eligible	38.8%	3

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: CDSN
Protein: p.Ala368=
Coding: c.1104A>G
MANE Select: NM_001264
dbSNP: rs1042126
Type: single nucleotide variant
Location: chr6:31116511 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 38.13

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

Similar variants

CDSN p.Ala368Gly Uncertain significance ★ same residue
CDSN p.Lys59Ter Pathogenic ★★ same type
CDSN p.Cys423Ser Uncertain significance ★★ same type
CDSN p.Gly335Ala Uncertain significance ★★ same type
CDSN p.Pro226Ser Uncertain significance ★★ same type
CDSN p.Pro282Thr Uncertain significance ★★ same type
CDSN p.Pro447Leu Uncertain significance ★★ same type
CDSN p.Pro471Leu 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/cdsn-p-ala368 (accessed [today's date]).

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