Is CDHR1 p.Pro812Ser (c.2434C>T) pathogenic?

CDHR1 p.Pro812Ser (c.2434C>T) is classified Benign/Likely benign in CDHR1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.2763); Low-frequency (popmax 4.35%, nfe).

How common is CDHR1 p.Pro812Ser (c.2434C>T) in the general population?

CDHR1 p.Pro812Ser (c.2434C>T) is low-frequency (popmax 4.35%, nfe) (gnomAD).

What do computational predictors say about CDHR1 p.Pro812Ser (c.2434C>T)?

AlphaMissense predicts likely benign (score 0.2763) — an in-silico prediction, not a clinical call.

CDHR1 p.Pro812Ser

c.2434C>T · rs45584033 · VCV262213

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2763 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.35%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2763	likely benign
REVEL	0.279	benign-leaning
SaProt	LLR -5.77	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 6	GERP 4.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 20 kb · p 0.035 · regional, not allelic
Overall
CADD	24.2	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 4.35% European (non-Finnish) · 51,314/1,179,664 alleles

Filtering AF 4.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.31%

Overall 3.77% 60,750/1,610,018 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	13%	8
Finnishnot grpmax-eligible	7.66%	13
European (non-Finnish)grpmax	4.35%	23
Remaining individualsnot grpmax-eligible	2.93%	34
Ashkenazi Jewishnot grpmax-eligible	2.22%	45
Admixed American	1.27%	79
South Asian	1.06%	94
Middle Eastern	0.677%	148
African / African-American	0.57%	175
East Asian	0.00446%	22,431

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CDHR1
Protein: p.Pro812Ser
Coding: c.2434C>T
MANE Select: NM_033100
dbSNP: rs45584033
Type: single nucleotide variant
Location: chr10:84214475 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79
Residue 812: the 'disordered' region

Full CDHR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDHR1 c.1168-1G>C Pathogenic/Likely pathogenic ★★ same type
CDHR1 c.1321-1G>A Likely pathogenic ★★ same type
CDHR1 c.1485+2T>C Pathogenic ★★ same type
CDHR1 c.1485+2T>G Pathogenic ★★ same type
CDHR1 c.1554-2A>C Pathogenic/Likely pathogenic ★★ same type
CDHR1 c.297+1G>T Pathogenic ★★ same type
CDHR1 c.525+1G>A Pathogenic ★★ same type
CDHR1 c.526-1G>A Likely pathogenic ★★ 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/cdhr1-p-pro812ser (accessed [today's date]).

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