Is CDON p.Val975Ile (c.2923G>A) pathogenic?

CDON p.Val975Ile (c.2923G>A) is classified Benign/Likely benign in CDON (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-05). AlphaMissense: likely benign (0.1041); Rare (popmax 0.976%, afr); Associated with holoprosencephaly 11.

What condition is associated with CDON p.Val975Ile (c.2923G>A)?

CDON p.Val975Ile (c.2923G>A) is associated with holoprosencephaly 11 (ClinVar).

How common is CDON p.Val975Ile (c.2923G>A) in the general population?

CDON p.Val975Ile (c.2923G>A) is rare (popmax 0.976%, afr) (gnomAD).

What do computational predictors say about CDON p.Val975Ile (c.2923G>A)?

AlphaMissense predicts likely benign (score 0.1041) — an in-silico prediction, not a clinical call.

CDON p.Val975Ile

c.2923G>A · rs113921147 · VCV539751

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1041 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.976%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

holoprosencephaly 11

Computational evidence

Protein change
AlphaMissense	0.1041	likely benign
REVEL	0.179	moderately benign-leaning
SaProt	LLR -7.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -0.12, phastCons 0.99
Regional constraint	o/e 0.93	unconstrained · MANE · 63 kb · p 0.0032 · regional, not allelic
Overall
CADD	21.9	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 0.976% African / African-American · 732/75,020 alleles

Filtering AF 0.917% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.894%

Overall 0.0611% 987/1,614,118 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.976%	102
Admixed American	0.222%	451
Remaining individualsnot grpmax-eligible	0.131%	762
Middle Eastern	0.0165%	6,062
South Asian	0.00988%	10,119
East Asian	0.00446%	22,441
European (non-Finnish)	0.00229%	43,704
Finnishnot grpmax-eligible	0.00156%	64,020

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.Val975Ile
Coding: c.2923G>A
MANE Select: NM_001378964
dbSNP: rs113921147
Type: single nucleotide variant
Location: chr11:125983944 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB

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-val975ile (accessed [today's date]).

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