Is DCHS1 p.Arg985Trp (c.2953C>T) pathogenic?

DCHS1 p.Arg985Trp (c.2953C>T) is classified Benign in DCHS1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-22). AlphaMissense: likely benign (0.1449); Low-frequency (popmax 1.99%, afr).

How common is DCHS1 p.Arg985Trp (c.2953C>T) in the general population?

DCHS1 p.Arg985Trp (c.2953C>T) is low-frequency (popmax 1.99%, afr) (gnomAD).

What do computational predictors say about DCHS1 p.Arg985Trp (c.2953C>T)?

AlphaMissense predicts likely benign (score 0.1449) — an in-silico prediction, not a clinical call.

DCHS1 p.Arg985Trp

c.2953C>T · rs138631004 · VCV776573

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1449 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.99%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1449	likely benign
REVEL	0.237	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 1.3	GERP -3.8, phastCons 0.02
Regional constraint	o/e 0.90	unconstrained · MANE · 18 kb · p 1.2e-10 · regional, not allelic
Overall
CADD	23.5	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 1.99% African / African-American · 1,442/72,308 alleles

Filtering AF 1.91% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.87%

Overall 0.12% 1,821/1,518,608 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.99%	50
Admixed American	0.186%	538
Remaining individualsnot grpmax-eligible	0.183%	546
East Asian	0.127%	787
Middle Eastern	0.123%	815
South Asian	0.013%	7,714
European (non-Finnish)	0.00982%	10,182
Ashkenazi Jewishnot grpmax-eligible	0.00402%	24,852

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.Arg985Trp
Coding: c.2953C>T
MANE Select: NM_003737
dbSNP: rs138631004
Type: single nucleotide variant
Location: chr11:6632559 (GRCh38)
Gene constraint: LOEUF 0.491 · pLI 0.33 · ClinGen HI 1/3 (gnomAD)
Residue 985: the cadherin 9 domain

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

Similar variants

DCHS1 p.Arg985Gln 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
DCHS1 p.Ala1460Pro 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-arg985trp (accessed [today's date]).

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