Is DCHS2 p.Arg734Ser (c.2202G>T) pathogenic?

DCHS2 p.Arg734Ser (c.2202G>T) is classified Uncertain significance in DCHS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: likely benign (0.1582); Very rare (popmax 0.00446%, eas).

How common is DCHS2 p.Arg734Ser (c.2202G>T) in the general population?

DCHS2 p.Arg734Ser (c.2202G>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DCHS2 p.Arg734Ser (c.2202G>T)?

AlphaMissense predicts likely benign (score 0.1582) — an in-silico prediction, not a clinical call.

DCHS2 p.Arg734Ser

c.2202G>T · VCV4009747

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1582 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1582	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.88	GERP -3.9
Regional constraint	o/e 1.03	unconstrained · MANE · 257 kb · p 0.063 · regional, not allelic
Overall
CADD	1.193	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,872 alleles

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

Overall 0.000137% 2/1,461,380 alleles · very rare

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: DCHS2
Protein: p.Arg734Ser
Coding: c.2202G>T
MANE Select: NM_001358235
Type: single nucleotide variant
Location: chr4:154377295 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Residue 734: the cadherin 6 domain

Full DCHS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCHS2 c.2053-13744T>A Uncertain significance ★ same type
DCHS2 c.2053-13798T>C Uncertain significance ★ same type
DCHS2 c.2053-13820G>A Uncertain significance ★ same type
DCHS2 c.2053-13834C>G Uncertain significance ★ same type
DCHS2 c.2244+3317A>T Uncertain significance ★ same type
DCHS2 c.2476+8901A>C Uncertain significance ★ same type
DCHS2 c.2477-1G>T Uncertain significance ★ same type
DCHS2 c.3730+872C>T 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/dchs2-p-arg734ser (accessed [today's date]).

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