Is DVL1 p.Pro104Ser (c.310C>T) pathogenic?

DVL1 p.Pro104Ser (c.310C>T) is classified Likely benign in DVL1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-01). AlphaMissense: likely benign (0.1032); Ultra-rare (popmax 0.0988%, sas).

How common is DVL1 p.Pro104Ser (c.310C>T) in the general population?

DVL1 p.Pro104Ser (c.310C>T) is ultra-rare (popmax 0.0988%, sas) (gnomAD).

What do computational predictors say about DVL1 p.Pro104Ser (c.310C>T)?

AlphaMissense predicts likely benign (score 0.1032) — an in-silico prediction, not a clinical call.

DVL1 p.Pro104Ser

c.310C>T · rs776308675 · VCV1989131

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1032 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0988%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1032	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -8.38	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 9.8	GERP 1.6, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 13 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	24.4	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 0.0988% South Asian · 88/89,024 alleles

Filtering AF 0.0821% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.076%

Overall 0.00627% 100/1,594,520 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0988%	1,012
Remaining individualsnot grpmax-eligible	0.00811%	12,324
African / African-American	0.00669%	14,942
European (non-Finnish)	0.000171%	585,370

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.Pro104Ser
Coding: c.310C>T
MANE Select: NM_001330311
dbSNP: rs776308675
Type: single nucleotide variant
Location: chr1:1342415 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 3 PDB
Residue 104: the 'disordered' region

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

Similar variants

DVL1 p.Pro104Leu Uncertain significance ★ ⚠ same residue
DVL1 p.Pro104= Likely benign ★ same residue
DVL1 p.Ala125Val Uncertain significance ★★ ⚠ same type
DVL1 p.Ala288Val Uncertain significance ★★ ⚠ same type
DVL1 p.Ala361Thr Uncertain significance ★★ ⚠ same type
DVL1 p.Ala368Val Uncertain significance ★★ ⚠ same type
DVL1 p.Ala667Pro Uncertain significance ★★ ⚠ same type
DVL1 p.Arg108Trp 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/dvl1-p-pro104ser (accessed [today's date]).

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