Is DCHS1 p.Pro2707Ser (c.8119C>T) pathogenic?

DCHS1 p.Pro2707Ser (c.8119C>T) is classified Conflicting classifications of pathogenicity in DCHS1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-07). AlphaMissense: ambiguous (0.4225); Ultra-rare (popmax 0.0894%, afr); Associated with Inborn genetic diseases.

What condition is associated with DCHS1 p.Pro2707Ser (c.8119C>T)?

DCHS1 p.Pro2707Ser (c.8119C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DCHS1 p.Pro2707Ser (c.8119C>T) in the general population?

DCHS1 p.Pro2707Ser (c.8119C>T) is ultra-rare (popmax 0.0894%, afr) (gnomAD).

What do computational predictors say about DCHS1 p.Pro2707Ser (c.8119C>T)?

AlphaMissense predicts ambiguous (score 0.4225) — an in-silico prediction, not a clinical call.

DCHS1 p.Pro2707Ser

c.8119C>T · rs150262490 · VCV2177159

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4225 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0894%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4225	ambiguous
REVEL	0.267	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 18 kb · p 1.2e-10 · regional, not allelic
Overall
CADD	25.3	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 0.0894% African / African-American · 67/74,908 alleles

Filtering AF 0.0722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.066%

Overall 0.00453% 73/1,612,882 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0894%	1,118
Remaining individualsnot grpmax-eligible	0.0032%	31,220
European (non-Finnish)	0.000339%	294,890

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.Pro2707Ser
Coding: c.8119C>T
MANE Select: NM_003737
dbSNP: rs150262490
Type: single nucleotide variant
Location: chr11:6623557 (GRCh38)
Gene constraint: LOEUF 0.491 · pLI 0.33 · ClinGen HI 1/3 (gnomAD)
Residue 2707: the cadherin 26 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.Pro2707= Likely benign ★ same residue
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

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-pro2707ser (accessed [today's date]).

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