Is CD33 p.Ala14Val (c.41C>T) pathogenic?

CD33 p.Ala14Val (c.41C>T) is classified Benign in CD33 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-13). AlphaMissense: likely benign (0.1529); Common (popmax 51.6%, amr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CD33 p.Ala14Val (c.41C>T)?

AlphaMissense predicts likely benign (score 0.1529) — an in-silico prediction, not a clinical call.

CD33 p.Ala14Val

Q: How common is CD33 p.Ala14Val (c.41C>T) in the general population?

CD33 p.Ala14Val (c.41C>T) is common (popmax 51.6%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.41C>T · rs12459419 · VCV1275129

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1529 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 51.6%, amr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1529	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -7.90	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 -1.6	GERP -0.3
Regional constraint	o/e 0.91	unconstrained · MANE · 15 kb · p 0.052 · regional, not allelic
Overall
CADD	15.1	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 51.6% Admixed American · 30,953/59,954 alleles

Filtering AF 51.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 50.9%

Overall 30.2% 486,842/1,612,814 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	51.6%	2
Finnishnot grpmax-eligible	36.2%	3
European (non-Finnish)	32.1%	3
Remaining individualsnot grpmax-eligible	27%	4
Ashkenazi Jewishnot grpmax-eligible	22.4%	4
East Asian	19%	5
Middle Eastern	18.8%	5
Amishnot grpmax-eligible	17.3%	6
South Asian	15.7%	6
African / African-American	8.2%	12

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: CD33
Protein: p.Ala14Val
Coding: c.41C>T
MANE Select: NM_001772
dbSNP: rs12459419
Type: single nucleotide variant
Location: chr19:51225221 (GRCh38)
Gene constraint: LOEUF 1.072 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.30 · 11 PDB
Residue 14: a UniProt-annotated variant site (in)

Full CD33 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD33 p.Asp51Asn Uncertain significance ★★ ⚠ same type
CD33 c.924+295A>G Benign ★★ same type
CD33 c.924+296C>T Benign ★★ same type
CD33 c.924+2T>C Benign ★★ same type
CD33 c.924+469G>C Benign ★★ same type
CD33 c.*201G>C Benign ★★ same type
CD33 p.Ala65Pro Benign ★★ ⚠ same type
CD33 p.Arg62Gln Likely benign ★★ 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/cd33-p-ala14val (accessed [today's date]).

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