Is CDHR2 p.Thr31Met (c.92C>T) pathogenic?

CDHR2 p.Thr31Met (c.92C>T) is classified Uncertain significance in CDHR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-02-08). AlphaMissense: likely benign (0.2881); Very rare (popmax 0.00446%, eas).

How common is CDHR2 p.Thr31Met (c.92C>T) in the general population?

CDHR2 p.Thr31Met (c.92C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CDHR2 p.Thr31Met (c.92C>T)?

AlphaMissense predicts likely benign (score 0.2881) — an in-silico prediction, not a clinical call.

CDHR2 p.Thr31Met

c.92C>T · rs750815475 · VCV2497709

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2881 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2881	likely benign
REVEL	0.153	moderately benign-leaning
SaProt	LLR -12.93	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.47 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.6	GERP -0.97, phastCons 0.29
Regional constraint	o/e 0.93	unconstrained · MANE · 19 kb · p 0.025 · regional, not allelic
Overall
CADD	20.7	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 0.00446% East Asian · 2/44,864 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000821% 12/1,461,704 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,432
African / African-American	0.00133%	75,032
South Asian	0.0011%	91,058
European (non-Finnish)	0.000678%	147,492

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: CDHR2
Protein: p.Thr31Met
Coding: c.92C>T
MANE Select: NM_017675
dbSNP: rs750815475
Type: single nucleotide variant
Location: chr5:176565711 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 2 PDB
Residue 31: the cadherin 1 domain; an α-helix

Full CDHR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDHR2 p.Ala1162Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala121Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala13Val Uncertain significance ★ ⚠ same type
CDHR2 p.Ala415Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala423Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala512Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala652Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala656Thr 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/cdhr2-p-thr31met (accessed [today's date]).

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