Is CAD p.Arg102His (c.305G>A) pathogenic?

CAD p.Arg102His (c.305G>A) is classified Uncertain significance in CAD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-22). AlphaMissense: likely benign (0.083); Very rare (popmax 0.00404%, afr).

How common is CAD p.Arg102His (c.305G>A) in the general population?

CAD p.Arg102His (c.305G>A) is very rare (popmax 0.00404%, afr) (gnomAD).

What do computational predictors say about CAD p.Arg102His (c.305G>A)?

AlphaMissense predicts likely benign (score 0.083) — an in-silico prediction, not a clinical call.

CAD p.Arg102His

c.305G>A · rs868201764 · VCV1911858

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.083 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00404%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.083	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	LLR -6.13	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 2.1	GERP -1.7, phastCons 0.017
Regional constraint	o/e 0.93	unconstrained · MANE · 5,475 bp · p 0.17 · regional, not allelic
Overall
CADD	14.99	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 0.00404% African / African-American · 3/74,210 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000794%

Overall 0.00157% 25/1,589,870 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00404%	24,737
Admixed American	0.00347%	28,848
East Asian	0.00229%	43,632
European (non-Finnish)	0.00154%	64,948
South Asian	0.00115%	86,626

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.Arg102His
Coding: c.305G>A
MANE Select: NM_004341
dbSNP: rs868201764
Type: single nucleotide variant
Location: chr2:27221300 (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

Similar variants

CAD p.Arg102Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
CAD p.Arg1789Ter Pathogenic ★★ same type
CAD p.Arg1810Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
CAD p.Arg191Ter Pathogenic ★★ same type
CAD p.Gln1604Ter Likely pathogenic ★★ same type
CAD p.Met33Arg Pathogenic ★★ same type
CAD c.1254+6G>A Uncertain significance ★★ same type
CAD c.2032-3C>T Uncertain significance ★★ same type

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-arg102his (accessed [today's date]).

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