Is DCHS1 p.Arg2021= (c.6063C>T) pathogenic?

DCHS1 p.Arg2021= (c.6063C>T) is classified Likely benign in DCHS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-02). Ultra-rare (popmax 0.0439%, sas).

How common is DCHS1 p.Arg2021= (c.6063C>T) in the general population?

DCHS1 p.Arg2021= (c.6063C>T) is ultra-rare (popmax 0.0439%, sas) (gnomAD).

DCHS1 p.Arg2021=

c.6063C>T · rs779485621 · VCV2995098

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0439%, sas)

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 0.16	GERP -3.5, phastCons 0.027
Overall
CADD	6.592	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0439% South Asian · 40/91,078 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00335% 54/1,613,642 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0439%	2,277
Admixed American	0.01%	10,000
African / African-American	0.004%	24,974
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Remaining individualsnot grpmax-eligible	0.0032%	31,230
European (non-Finnish)	0.00017%	589,946

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.Arg2021=
Coding: c.6063C>T
MANE Select: NM_003737
dbSNP: rs779485621
Type: single nucleotide variant
Location: chr11:6626976 (GRCh38)
Gene constraint: LOEUF 0.491 · pLI 0.33 · ClinGen HI 1/3 (gnomAD)
Residue 2021: the cadherin 19 domain

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

Similar variants

DCHS1 p.Arg2021Cys Uncertain significance ★★ same residue
DCHS1 p.Arg2021His Uncertain significance ★★ ⚠ same residue
DCHS1 p.Arg2141Ter Pathogenic/Likely pathogenic ★★ same type
DCHS1 p.Arg2330Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
DCHS1 p.Ala1241Val Uncertain significance ★★ same type
DCHS1 p.Ala1325Ser Uncertain significance ★★ ⚠ same type
DCHS1 p.Ala142Thr Uncertain significance ★★ ⚠ same type
DCHS1 p.Ala1454Val 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/dchs1-p-arg2021 (accessed [today's date]).

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