Is CAD p.Arg102Cys (c.304C>T) pathogenic?

CAD p.Arg102Cys (c.304C>T) is classified Conflicting classifications of pathogenicity in CAD (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-09). AlphaMissense: likely benign (0.0877); Very rare (popmax 0.00461%, sas); Associated with Inborn genetic diseases.

What condition is associated with CAD p.Arg102Cys (c.304C>T)?

CAD p.Arg102Cys (c.304C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CAD p.Arg102Cys (c.304C>T) in the general population?

CAD p.Arg102Cys (c.304C>T) is very rare (popmax 0.00461%, sas) (gnomAD).

What do computational predictors say about CAD p.Arg102Cys (c.304C>T)?

AlphaMissense predicts likely benign (score 0.0877) — an in-silico prediction, not a clinical call.

CAD p.Arg102Cys

c.304C>T · rs190254898 · VCV1504932

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0877 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00461%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0877	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -5.39	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 -0.63	GERP -4.3
Regional constraint	o/e 0.93	unconstrained · MANE · 5,475 bp · p 0.17 · regional, not allelic
Overall
CADD	7.564	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 0.00461% South Asian · 4/86,734 alleles

Filtering AF 0.00148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000926%

Overall 0.000566% 9/1,590,984 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00461%	21,684
East Asian	0.00229%	43,636
African / African-American	0.00135%	74,336
European (non-Finnish)	0.000257%	389,845

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: CAD
Protein: p.Arg102Cys
Coding: c.304C>T
MANE Select: NM_004341
dbSNP: rs190254898
Type: single nucleotide variant
Location: chr2:27221299 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB
Residue 102: the 'gatase (glutamine amidotransferase)' region

Full CAD 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

CAD p.Arg102His Uncertain significance ★ ⚠ same residue
CAD c.6480+6T>C Uncertain significance ★★ same condition
CAD p.Ala1527Thr Uncertain significance ★★ ⚠ same condition
CAD p.Ala1769Thr Uncertain significance ★★ ⚠ same condition
CAD p.Ala1824Ser Uncertain significance ★★ ⚠ same condition
CAD p.Ala495Pro Uncertain significance ★★ ⚠ same condition
CAD p.Ala608Thr Uncertain significance ★★ ⚠ same condition
CAD p.Arg1075His 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/cad-p-arg102cys (accessed [today's date]).

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