Is DCHS2 p.Val1072Phe (c.3214G>T) pathogenic?

DCHS2 p.Val1072Phe (c.3214G>T) is classified Likely benign in DCHS2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-01). AlphaMissense: likely benign (0.0976); Rare (popmax 0.398%, afr); Associated with DCHS2-related disorder.

What condition is associated with DCHS2 p.Val1072Phe (c.3214G>T)?

DCHS2 p.Val1072Phe (c.3214G>T) is associated with DCHS2-related disorder (ClinVar).

How common is DCHS2 p.Val1072Phe (c.3214G>T) in the general population?

DCHS2 p.Val1072Phe (c.3214G>T) is rare (popmax 0.398%, afr) (gnomAD).

What do computational predictors say about DCHS2 p.Val1072Phe (c.3214G>T)?

AlphaMissense predicts likely benign (score 0.0976) — an in-silico prediction, not a clinical call.

DCHS2 p.Val1072Phe

c.3214G>T · rs74422312 · VCV3051211

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0976 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.398%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

DCHS2-related disorder

Computational evidence

Protein change
AlphaMissense	0.0976	likely benign
REVEL	0.052	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 -7.2	GERP -5.5
Regional constraint	o/e 1.03	unconstrained · MANE · 257 kb · p 0.063 · regional, not allelic
Overall
CADD	1.337	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 0.398% African / African-American · 299/75,050 alleles

Filtering AF 0.361% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.347%

Overall 0.0208% 336/1,614,172 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.398%	251
Middle Eastern	0.115%	866
Remaining individualsnot grpmax-eligible	0.0288%	3,473
Admixed American	0.0117%	8,576
European (non-Finnish)	0.000424%	236,002

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.Val1072Phe
Coding: c.3214G>T
MANE Select: NM_001358235
dbSNP: rs74422312
Type: single nucleotide variant
Location: chr4:154332994 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Residue 1072: the cadherin 9 domain

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

Disease context

DCHS2-related disorder

Similar variants

DCHS2 p.Val1072Ile Uncertain significance ★ ⚠ same residue
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

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-val1072phe (accessed [today's date]).

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