Is DCHS1 p.Ala841= (c.2523G>A) pathogenic?

DCHS1 p.Ala841= (c.2523G>A) is classified Benign/Likely benign in DCHS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-20). Ultra-rare (popmax 0.078%, eas); Associated with Inborn genetic diseases.

What condition is associated with DCHS1 p.Ala841= (c.2523G>A)?

DCHS1 p.Ala841= (c.2523G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DCHS1 p.Ala841= (c.2523G>A) in the general population?

DCHS1 p.Ala841= (c.2523G>A) is ultra-rare (popmax 0.078%, eas) (gnomAD).

DCHS1 p.Ala841=

c.2523G>A · rs186255064 · VCV1640958

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.078%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.5	GERP -3.8
Overall
CADD	6.071	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.078% East Asian · 35/44,880 alleles

Filtering AF 0.0576% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0506%

Overall 0.00291% 47/1,613,876 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.078%	1,282
Finnishnot grpmax-eligible	0.00781%	12,800
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.000509%	196,634

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.Ala841=
Coding: c.2523G>A
MANE Select: NM_003737
dbSNP: rs186255064
Type: single nucleotide variant
Location: chr11:6632989 (GRCh38)
Gene constraint: LOEUF 0.491 · pLI 0.33 · ClinGen HI 1/3 (gnomAD)
Residue 841: the cadherin 8 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.Ala841Val Uncertain significance ★★ ⚠ same residue
DCHS1 p.Ala841Ser Uncertain significance ★ ⚠ 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

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-ala841 (accessed [today's date]).

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