Is DVL1 p.Ala91Val (c.272C>T) pathogenic?

DVL1 p.Ala91Val (c.272C>T) is classified Benign/Likely benign in DVL1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0712); Low-frequency (popmax 3.5%, amr); Associated with autosomal dominant Robinow syndrome 1.

What condition is associated with DVL1 p.Ala91Val (c.272C>T)?

DVL1 p.Ala91Val (c.272C>T) is associated with autosomal dominant Robinow syndrome 1, autosomal dominant Robinow syndrome 2 (ClinVar).

How common is DVL1 p.Ala91Val (c.272C>T) in the general population?

DVL1 p.Ala91Val (c.272C>T) is low-frequency (popmax 3.5%, amr) (gnomAD).

What do computational predictors say about DVL1 p.Ala91Val (c.272C>T)?

AlphaMissense predicts likely benign (score 0.0712) — an in-silico prediction, not a clinical call.

DVL1 p.Ala91Val

c.272C>T · rs145496306 · VCV788936

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0712 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.5%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal dominant Robinow syndrome 1

Computational evidence

Protein change
AlphaMissense	0.0712	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -7.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -2.2, phastCons 0.28
Regional constraint	o/e 1.15	unconstrained · MANE · 13 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	13.37	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 3.5% Admixed American · 2,088/59,650 alleles

Filtering AF 3.38% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.32%

Overall 0.161% 2,594/1,607,914 alleles · low-frequency

Ancestry group	Frequency	1 in
Admixed Americangrpmax	3.5%	29
Middle Eastern	0.132%	756
Remaining individualsnot grpmax-eligible	0.114%	876
South Asian	0.0884%	1,131
African / African-American	0.044%	2,272
European (non-Finnish)	0.0258%	3,876
Finnishnot grpmax-eligible	0.0148%	6,776
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,478

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: DVL1
Protein: p.Ala91Val
Coding: c.272C>T
MANE Select: NM_001330311
dbSNP: rs145496306
Type: single nucleotide variant
Location: chr1:1342453 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 3 PDB
Residue 91: the 'disordered' region

Full DVL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant Robinow syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal dominant Robinow syndrome 2

Similar variants

DVL1 p.Ala91= Uncertain significance ★ same residue
DVL1 p.Ala288Val Uncertain significance ★★ ⚠ same condition
DVL1 p.Arg116Gln Uncertain significance ★★ ⚠ same condition
DVL1 p.Arg128Cys Uncertain significance ★★ ⚠ same condition
DVL1 p.Arg40Gly Uncertain significance ★★ ⚠ same condition
DVL1 p.Glu85Asp Uncertain significance ★★ ⚠ same condition
DVL1 p.Ser246Phe Uncertain significance ★★ ⚠ same condition
DVL1 p.Thr253Met Uncertain significance ★★ ⚠ 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/dvl1-p-ala91val (accessed [today's date]).

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