Is DCHS2 p.Ala1626Val (c.4877C>T) pathogenic?

DCHS2 p.Ala1626Val (c.4877C>T) is classified Benign in DCHS2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-20). AlphaMissense: likely benign (0.0858); Low-frequency (popmax 2.03%, afr); Associated with DCHS2-related disorder.

What condition is associated with DCHS2 p.Ala1626Val (c.4877C>T)?

DCHS2 p.Ala1626Val (c.4877C>T) is associated with DCHS2-related disorder (ClinVar).

How common is DCHS2 p.Ala1626Val (c.4877C>T) in the general population?

DCHS2 p.Ala1626Val (c.4877C>T) is low-frequency (popmax 2.03%, afr) (gnomAD).

What do computational predictors say about DCHS2 p.Ala1626Val (c.4877C>T)?

AlphaMissense predicts likely benign (score 0.0858) — an in-silico prediction, not a clinical call.

DCHS2 p.Ala1626Val

c.4877C>T · rs56277131 · VCV3041054

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0858 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.03%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

DCHS2-related disorder

Computational evidence

Protein change
AlphaMissense	0.0858	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 257 kb · p 0.063 · regional, not allelic
Overall
CADD	10.53	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.03% African / African-American · 1,523/75,002 alleles

Filtering AF 1.95% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.91%

Overall 0.108% 1,743/1,614,016 alleles · low-frequency exomes 837/1,461,838 · genomes 906/152,178 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.03%	49
Middle Eastern	0.181%	551
Remaining individualsnot grpmax-eligible	0.128%	781
Admixed American	0.123%	811
Ashkenazi Jewishnot grpmax-eligible	0.0439%	2,277
European (non-Finnish)	0.00347%	28,780
South Asian	0.0011%	91,070

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: DCHS2
Protein: p.Ala1626Val
Coding: c.4877C>T
MANE Select: NM_001358235
dbSNP: rs56277131
Type: single nucleotide variant
Location: chr4:154320522 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Residue 1626: the cadherin 15 domain

Full DCHS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DCHS2-related disorder

Similar variants

DCHS2 c.2477-1G>T Uncertain significance ★ same condition
DCHS2 p.Ala952Thr Uncertain significance same condition
DCHS2 p.Ile802Val Uncertain significance ⚠ same condition
DCHS2 p.Ser1397Phe Uncertain significance ⚠ same condition
DCHS2 c.2053-13755G>A Likely benign same condition
DCHS2 c.2053-13815C>T Benign same condition
DCHS2 c.2244+3329T>C Benign same condition
DCHS2 c.2477-8381C>T Benign 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/dchs2-p-ala1626val (accessed [today's date]).

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