Is DVL2 p.Gln554= (c.1662A>G) pathogenic?

DVL2 p.Gln554= (c.1662A>G) is classified Benign in DVL2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-06-22). Common (popmax 69.3%, mid) — too common for a highly-penetrant pathogenic allele.

DVL2 p.Gln554=

Q: How common is DVL2 p.Gln554= (c.1662A>G) in the general population?

DVL2 p.Gln554= (c.1662A>G) is common (popmax 69.3%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1662A>G · rs35594616 · VCV1243912

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 69.3%, mid) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP -4, phastCons 0.99
Overall
CADD	4.545	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 69.3% Middle Eastern · 4,165/6,008 alleles

Filtering AF 67.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 66.8%

Overall 61.1% 982,127/1,606,304 alleles · common exomes 895,551/1,454,426 · genomes 86,576/151,878 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	69.3%	1
Finnishnot grpmax-eligible	66.4%	2
South Asian	65.7%	2
Amishnot grpmax-eligible	62.8%	2
European (non-Finnish)	62.7%	2
Remaining individualsnot grpmax-eligible	60.1%	2
Ashkenazi Jewishnot grpmax-eligible	59.6%	2
Admixed American	51.5%	2
East Asian	46.2%	2
African / African-American	43.3%	2

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: DVL2
Protein: p.Gln554=
Coding: c.1662A>G
MANE Select: NM_004422
dbSNP: rs35594616
Type: single nucleotide variant
Location: chr17:7226521 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.37 · 16 PDB

Full DVL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DVL2 c.1035-8C>T Benign ★★ same type
DVL2 c.1544-16T>C Benign ★★ same type
DVL2 p.Leu317= Benign ★★ same type
DVL2 p.Ser207= Benign ★★ same type
DVL2 p.Thr250= Likely benign ★★ same type
DVL2 p.Ala114Val Uncertain significance ★ ⚠ same type
DVL2 p.Ala384Val Uncertain significance ★ ⚠ same type
DVL2 p.Ala385Thr 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/dvl2-p-gln554 (accessed [today's date]).

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