Is CAD p.Pro55Ser (c.163C>T) pathogenic?

CAD p.Pro55Ser (c.163C>T) is classified Uncertain significance in CAD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-01). AlphaMissense: likely pathogenic (0.7374); Ultra-rare (popmax 0.0156%, eas); Associated with Inborn genetic diseases.

What condition is associated with CAD p.Pro55Ser (c.163C>T)?

CAD p.Pro55Ser (c.163C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CAD p.Pro55Ser (c.163C>T) in the general population?

CAD p.Pro55Ser (c.163C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about CAD p.Pro55Ser (c.163C>T)?

AlphaMissense predicts likely pathogenic (score 0.7374) — an in-silico prediction, not a clinical call.

CAD p.Pro55Ser

c.163C>T · rs1172957816 · VCV1351807

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7374 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7374	likely pathogenic
REVEL	0.926	moderately pathogenic-leaning
SaProt	LLR -9.27	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 5,475 bp · p 0.17 · regional, not allelic
Overall
CADD	28.1	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 0.0156% East Asian · 7/44,760 alleles

Filtering AF 0.00728% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00516%

Overall 0.00149% 24/1,612,912 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,394
African / African-American	0.00267%	37,441
South Asian	0.0022%	45,468
European (non-Finnish)	0.0011%	90,720

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.Pro55Ser
Coding: c.163C>T
MANE Select: NM_004341
dbSNP: rs1172957816
Type: single nucleotide variant
Location: chr2:27217957 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB
Residue 55: 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 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
CAD p.Arg1181Gln 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-pro55ser (accessed [today's date]).

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