Is DCHS1 p.Pro1970Ser (c.5908C>T) pathogenic?

DCHS1 p.Pro1970Ser (c.5908C>T) is classified Uncertain significance in DCHS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-07). AlphaMissense: likely benign (0.0824); Very rare (popmax 0.000763%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DCHS1 p.Pro1970Ser (c.5908C>T)?

DCHS1 p.Pro1970Ser (c.5908C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DCHS1 p.Pro1970Ser (c.5908C>T) in the general population?

DCHS1 p.Pro1970Ser (c.5908C>T) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about DCHS1 p.Pro1970Ser (c.5908C>T)?

AlphaMissense predicts likely benign (score 0.0824) — an in-silico prediction, not a clinical call.

DCHS1 p.Pro1970Ser

c.5908C>T · rs1435983023 · VCV1523807

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0824 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0824	likely benign
REVEL	0.114	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 18 kb · p 1.2e-10 · regional, not allelic
Overall
CADD	21.8	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 0.000763% European (non-Finnish) · 9/1,179,310 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000558% 9/1,612,550 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: DCHS1
Protein: p.Pro1970Ser
Coding: c.5908C>T
MANE Select: NM_003737
dbSNP: rs1435983023
Type: single nucleotide variant
Location: chr11:6627131 (GRCh38)
Gene constraint: LOEUF 0.491 · pLI 0.33 · ClinGen HI 1/3 (gnomAD)
Residue 1970: the cadherin 19 domain

Full DCHS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DCHS1 p.Ala1454Val Uncertain significance ★★ ⚠ same condition
DCHS1 p.Ala1460Pro Uncertain significance ★★ same condition
DCHS1 p.Ala1490Glu Uncertain significance ★★ ⚠ same condition
DCHS1 p.Ala1547Gly Uncertain significance ★★ ⚠ same condition
DCHS1 p.Ala1564Gly Uncertain significance ★★ ⚠ same condition
DCHS1 p.Ala1673Val Uncertain significance ★★ same condition
DCHS1 p.Ala1754Ser Uncertain significance ★★ ⚠ same condition
DCHS1 p.Ala1754Val Uncertain significance ★★ ⚠ same condition

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/dchs1-p-pro1970ser (accessed [today's date]).

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