Is CD96 c.807+14A>C pathogenic?

CD96 c.807+14A>C is classified Benign/Likely benign in CD96 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-23). Rare (popmax 0.539%, amr); Associated with C syndrome.

What condition is associated with CD96 c.807+14A>C?

CD96 c.807+14A>C is associated with C syndrome (ClinVar).

How common is CD96 c.807+14A>C in the general population?

CD96 c.807+14A>C is rare (popmax 0.539%, amr) (gnomAD).

CD96 c.807+14A>C

rs144245769 · VCV1646850

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.539%, amr)

Conditions

C syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +14	near-intronic (+14 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 1.6, phastCons 0.74
Non-coding constraint	Z -1.27	1 kb window · o/e 1.10 · regional · uncalibrated
Overall
CADD	12.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.539% Admixed American · 323/59,920 alleles

Filtering AF 0.491% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.472%

Overall 0.209% 3,236/1,549,908 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.539%	186
European (non-Finnish)	0.247%	405
Remaining individualsnot grpmax-eligible	0.171%	586
African / African-American	0.0461%	2,167
Middle Eastern	0.0169%	5,932
Ashkenazi Jewishnot grpmax-eligible	0.00686%	14,580
Finnishnot grpmax-eligible	0.00313%	31,915

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: CD96
Coding: c.807+14A>C
MANE Select: NM_005816
dbSNP: rs144245769
Type: single nucleotide variant
Location: chr3:111585392 (GRCh38)
Gene constraint: LOEUF 1.16 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.81 · 1 PDB

Full CD96 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

C syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD96 c.1249+1G>A Uncertain significance ★★ same condition
CD96 c.1321+1G>A Likely pathogenic ★ same condition
CD96 c.807+2T>A Likely pathogenic ★ same condition
CD96 c.1181-12T>C Uncertain significance ★ same condition
CD96 p.Asn464Asp Uncertain significance ★ ⚠ same condition
CD96 p.Asp265Gly Uncertain significance ★ ⚠ same condition
CD96 p.Cys515Arg Uncertain significance ★ ⚠ same condition
CD96 p.Leu342Gln 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/cd96-c-807-plus-14a-c (accessed [today's date]).

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