Is CDON p.His311Tyr (c.931C>T) pathogenic?

CDON p.His311Tyr (c.931C>T) is classified Uncertain significance in CDON (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-27). AlphaMissense: likely benign (0.2194); Ultra-rare (popmax 0.0173%, afr); Associated with Inborn genetic diseases.

What condition is associated with CDON p.His311Tyr (c.931C>T)?

CDON p.His311Tyr (c.931C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDON p.His311Tyr (c.931C>T) in the general population?

CDON p.His311Tyr (c.931C>T) is ultra-rare (popmax 0.0173%, afr) (gnomAD).

What do computational predictors say about CDON p.His311Tyr (c.931C>T)?

AlphaMissense predicts likely benign (score 0.2194) — an in-silico prediction, not a clinical call.

CDON p.His311Tyr

c.931C>T · rs369439584 · VCV2249045

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2194 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2194	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	LLR -7.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.70 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.5	GERP 0.14, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 63 kb · p 0.0032 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0173% African / African-American · 13/75,032 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00812%

Overall 0.00149% 24/1,613,688 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0176%	5,681
African / African-Americangrpmax	0.0173%	5,772

Remaining individuals 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: CDON
Protein: p.His311Tyr
Coding: c.931C>T
MANE Select: NM_001378964
dbSNP: rs369439584
Type: single nucleotide variant
Location: chr11:126015508 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 3 PDB
Residue 311: the ig-like c2-type 4 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDON p.His311Asn Uncertain significance ★ ⚠ same residue
CDON p.Ala1099Val Uncertain significance ★★ ⚠ same condition
CDON p.Ala495Val Uncertain significance ★★ ⚠ same condition
CDON p.Arg157Trp Uncertain significance ★★ ⚠ same condition
CDON p.Arg760Leu Uncertain significance ★★ ⚠ same condition
CDON p.Asn1222Asp Uncertain significance ★★ ⚠ same condition
CDON p.Gln1008Lys Uncertain significance ★★ ⚠ same condition
CDON p.Glu663Asp 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-his311tyr (accessed [today's date]).

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