Is DCHS1 p.Ala181Val (c.542C>T) pathogenic?

DCHS1 p.Ala181Val (c.542C>T) is classified Likely benign in DCHS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-22). AlphaMissense: likely benign (0.0793); Rare (popmax 0.14%, amr).

How common is DCHS1 p.Ala181Val (c.542C>T) in the general population?

DCHS1 p.Ala181Val (c.542C>T) is rare (popmax 0.14%, amr) (gnomAD).

What do computational predictors say about DCHS1 p.Ala181Val (c.542C>T)?

AlphaMissense predicts likely benign (score 0.0793) — an in-silico prediction, not a clinical call.

DCHS1 p.Ala181Val

c.542C>T · rs778581851 · VCV2978626

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0793 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.14%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0793	likely benign
REVEL	0.059	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 8.4	GERP 0.85, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 18 kb · p 1.2e-10 · regional, not allelic
Overall
CADD	20.4	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 0.14% Admixed American · 84/60,012 alleles

Filtering AF 0.116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.107%

Overall 0.00626% 101/1,613,880 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.14%	714
Remaining individualsnot grpmax-eligible	0.0016%	62,464
European (non-Finnish)	0.00127%	78,660
South Asian	0.0011%	91,094

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.Ala181Val
Coding: c.542C>T
MANE Select: NM_003737
dbSNP: rs778581851
Type: single nucleotide variant
Location: chr11:6641072 (GRCh38)
Gene constraint: LOEUF 0.491 · pLI 0.33 · ClinGen HI 1/3 (gnomAD)
Residue 181: the cadherin 2 domain; a β-strand

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

Similar variants

DCHS1 p.Ala181= Likely benign ★ 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-ala181val (accessed [today's date]).

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