Is CDR2 p.Ala178Thr (c.532G>A) pathogenic?

CDR2 p.Ala178Thr (c.532G>A) is classified Uncertain significance in CDR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-06). AlphaMissense: ambiguous (0.4933); Very rare (popmax 0.00935%, afr).

How common is CDR2 p.Ala178Thr (c.532G>A) in the general population?

CDR2 p.Ala178Thr (c.532G>A) is very rare (popmax 0.00935%, afr) (gnomAD).

What do computational predictors say about CDR2 p.Ala178Thr (c.532G>A)?

AlphaMissense predicts ambiguous (score 0.4933) — an in-silico prediction, not a clinical call.

CDR2 p.Ala178Thr

c.532G>A · VCV3489726

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4933 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4933	ambiguous
REVEL	0.148	moderately benign-leaning
SaProt	LLR -5.65	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 27 kb · p 0.028 · regional, not allelic
Overall
CADD	24.0	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 0.00935% African / African-American · 7/74,884 alleles

Filtering AF 0.00605% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00565%

Overall 0.00601% 97/1,613,174 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,698
European (non-Finnish)	0.00737%	13,562
Admixed American	0.00167%	59,988
Remaining individualsnot grpmax-eligible	0.0016%	62,482
South Asian	0.0011%	91,044

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: CDR2
Protein: p.Ala178Thr
Coding: c.532G>A
MANE Select: NM_001802
Type: single nucleotide variant
Location: chr16:22347798 (GRCh38)
Gene constraint: LOEUF 0.879 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.84

Full CDR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDR2 p.Ala107Val Uncertain significance ★ ⚠ same type
CDR2 p.Ala155Thr Uncertain significance ★ ⚠ same type
CDR2 p.Ala252Pro Uncertain significance ★ ⚠ same type
CDR2 p.Ala319Ser Uncertain significance ★ ⚠ same type
CDR2 p.Ala355Thr Uncertain significance ★ ⚠ same type
CDR2 p.Ala394Thr Uncertain significance ★ ⚠ same type
CDR2 p.Arg213Gln Uncertain significance ★ ⚠ same type
CDR2 p.Arg216Gln 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/cdr2-p-ala178thr (accessed [today's date]).

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