Is CDON p.Glu162Lys (c.484G>A) pathogenic?

CDON p.Glu162Lys (c.484G>A) is classified Benign in CDON (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.189); Common (popmax 13.7%, amr) — too common for a highly-penetrant pathogenic allele; Associated with holoprosencephaly 11.

What condition is associated with CDON p.Glu162Lys (c.484G>A)?

CDON p.Glu162Lys (c.484G>A) is associated with holoprosencephaly 11 (ClinVar).

What do computational predictors say about CDON p.Glu162Lys (c.484G>A)?

AlphaMissense predicts likely benign (score 0.189) — an in-silico prediction, not a clinical call.

CDON p.Glu162Lys

Q: How common is CDON p.Glu162Lys (c.484G>A) in the general population?

CDON p.Glu162Lys (c.484G>A) is common (popmax 13.7%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.484G>A · rs3740909 · VCV260800

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.189 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 13.7%, amr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

holoprosencephaly 11

Computational evidence

Protein change
AlphaMissense	0.189	likely benign
REVEL	0.178	moderately benign-leaning
SaProt	LLR -5.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.9	GERP 0.088, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 63 kb · p 0.0032 · regional, not allelic
Overall
CADD	20.8	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 13.7% Admixed American · 8,224/59,974 alleles

Filtering AF 13.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.4%

Overall 9.31% 150,190/1,613,658 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	13.7%	7
Finnishnot grpmax-eligible	12.6%	8
East Asian	12.3%	8
South Asian	11.6%	9
African / African-American	11.3%	9
Ashkenazi Jewishnot grpmax-eligible	10.2%	10
Remaining individualsnot grpmax-eligible	9.77%	10
European (non-Finnish)	8.46%	12
Middle Eastern	7.24%	14
Amishnot grpmax-eligible	3.51%	29

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: CDON
Protein: p.Glu162Lys
Coding: c.484G>A
MANE Select: NM_001378964
dbSNP: rs3740909
Type: single nucleotide variant
Location: chr11:126019631 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB
Residue 162: a disulfide bond; a UniProt-annotated variant site (in); the ig-like c2-type 2 domain

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

Disease context

holoprosencephaly 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDON c.3276+1G>T Uncertain significance ★★ same condition
CDON c.640+1G>A Uncertain significance ★★ same condition
CDON c.*1805A>G Uncertain significance ★★ same condition
CDON c.*1816C>T Uncertain significance ★★ same condition
CDON c.*2349A>C Uncertain significance ★★ same condition
CDON c.*2377T>C Uncertain significance ★★ same condition
CDON c.*2760A>G Uncertain significance ★★ same condition
CDON p.Ala1099Val 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/cdon-p-glu162lys (accessed [today's date]).

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