Is DYNAP p.Asp2Glu (c.6C>G) pathogenic?

DYNAP p.Asp2Glu (c.6C>G) is classified Uncertain significance in DYNAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-07). AlphaMissense: likely benign (0.226); Very rare (popmax 0.0022%, sas).

How common is DYNAP p.Asp2Glu (c.6C>G) in the general population?

DYNAP p.Asp2Glu (c.6C>G) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about DYNAP p.Asp2Glu (c.6C>G)?

AlphaMissense predicts likely benign (score 0.226) — an in-silico prediction, not a clinical call.

DYNAP p.Asp2Glu

c.6C>G · rs776289970 · VCV2495424

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.226 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.226	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -5.86	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 -1.8	GERP -2.6
Regional constraint	o/e 1.14	unconstrained · MANE · 6,859 bp · p 0.034 · regional, not allelic
Overall
CADD	11.48	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D28E vs ClinVar D2E) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/90,980 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,460,676 alleles · very rare

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: DYNAP
Protein: p.Asp2Glu
Coding: c.6C>G
MANE Select: NM_173629
dbSNP: rs776289970
Type: single nucleotide variant
Location: chr18:54591288 (GRCh38)
Gene constraint: LOEUF 1.221 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 60.24

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

Similar variants

DYNAP c.13A>C Uncertain significance ★ ⚠ same type
DYNAP c.14T>C Uncertain significance ★ same type
DYNAP c.20G>A Uncertain significance ★ ⚠ same type
DYNAP c.28C>A Uncertain significance ★ ⚠ same type
DYNAP c.-29G>C Uncertain significance ★ ⚠ same type
DYNAP p.Ala158Asp Uncertain significance ★ ⚠ same type
DYNAP p.Ala169Thr Uncertain significance ★ ⚠ same type
DYNAP p.Ala29Pro 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/dynap-p-asp2glu (accessed [today's date]).

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