Is CDSN p.Val255= (c.765G>A) pathogenic?

CDSN p.Val255= (c.765G>A) is classified Likely benign in CDSN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-01). Ultra-rare (popmax 0.0594%, nfe).

How common is CDSN p.Val255= (c.765G>A) in the general population?

CDSN p.Val255= (c.765G>A) is ultra-rare (popmax 0.0594%, nfe) (gnomAD).

CDSN p.Val255=

c.765G>A · rs150163828 · VCV2164867

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0594%, nfe)

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 -2.2
Overall
CADD	6.941	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0594% European (non-Finnish) · 701/1,179,976 alleles

Filtering AF 0.0557% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.0478% 771/1,613,980 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0719%	1,392
European (non-Finnish)grpmax	0.0594%	1,683
Remaining individualsnot grpmax-eligible	0.0256%	3,905
Admixed American	0.005%	20,003
African / African-American	0.004%	24,979
East Asian	0.00223%	44,884
South Asian	0.0011%	91,088

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val255=
Coding: c.765G>A
MANE Select: NM_001264
dbSNP: rs150163828
Type: single nucleotide variant
Location: chr6:31116850 (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.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
CDSN p.Ser159Gly 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-val255 (accessed [today's date]).

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