Is CDHR5 p.Pro720Ser (c.2158C>T) pathogenic?

CDHR5 p.Pro720Ser (c.2158C>T) is classified Uncertain significance in CDHR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.0776); Very rare (popmax 0.00574%, sas).

How common is CDHR5 p.Pro720Ser (c.2158C>T) in the general population?

CDHR5 p.Pro720Ser (c.2158C>T) is very rare (popmax 0.00574%, sas) (gnomAD).

What do computational predictors say about CDHR5 p.Pro720Ser (c.2158C>T)?

AlphaMissense predicts likely benign (score 0.0776) — an in-silico prediction, not a clinical call.

CDHR5 p.Pro720Ser

c.2158C>T · VCV3489110

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0776 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00574%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0776	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -6.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.25	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -1.3	GERP -3.1
Regional constraint	o/e 1.11	unconstrained · MANE · 7,548 bp · p 0.00028 · regional, not allelic
Overall
CADD	0.386	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00574% South Asian · 4/69,686 alleles

Filtering AF 0.00194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0011%

Overall 0.000342% 5/1,460,844 alleles · very rare exomes 4/1,308,656 · genomes 1/152,188 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00574%	17,422
European (non-Finnish)	8.97e-05%	1,114,754

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: CDHR5
Protein: p.Pro720Ser
Coding: c.2158C>T
MANE Select: NM_021924
Type: single nucleotide variant
Location: chr11:617731 (GRCh38)
Gene constraint: LOEUF 1.479 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.84 · 1 PDB
Residue 720: the 'mediates interaction with ush1c and myo7b and is required for proper localization to microvilli tips and function in microvilli organization' region

Full CDHR5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDHR5 p.Arg182His Benign ★★ same type
CDHR5 p.Gly298= Benign ★★ same type
CDHR5 p.Ala151Pro Uncertain significance ★ ⚠ same type
CDHR5 p.Ala171Thr Uncertain significance ★ ⚠ same type
CDHR5 p.Ala230Thr Uncertain significance ★ ⚠ same type
CDHR5 p.Ala347Val Uncertain significance ★ ⚠ same type
CDHR5 p.Ala364Val Uncertain significance ★ ⚠ same type
CDHR5 p.Ala369Val 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/cdhr5-p-pro720ser (accessed [today's date]).

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