Is DERA p.Arg80Gly (c.238C>G) pathogenic?

DERA p.Arg80Gly (c.238C>G) is classified Uncertain significance in DERA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-20). AlphaMissense: ambiguous (0.5099); Very rare (popmax 0.00401%, afr).

How common is DERA p.Arg80Gly (c.238C>G) in the general population?

DERA p.Arg80Gly (c.238C>G) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about DERA p.Arg80Gly (c.238C>G)?

AlphaMissense predicts ambiguous (score 0.5099) — an in-silico prediction, not a clinical call.

DERA p.Arg80Gly

c.238C>G · rs369289804 · VCV2255886

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5099 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Computational evidence

Protein change
AlphaMissense	0.5099	ambiguous
REVEL	0.299	indeterminate
SaProt	LLR -12.72	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 0.87, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 125 kb · p 0.71 · regional, not allelic
Overall
CADD	23.5	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 0.00401% African / African-American · 3/74,720 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000496%

Overall 0.000187% 3/1,603,174 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: DERA
Protein: p.Arg80Gly
Coding: c.238C>G
MANE Select: NM_015954
dbSNP: rs369289804
Type: single nucleotide variant
Location: chr12:15958296 (GRCh38)
Gene constraint: LOEUF 0.658 · pLI 0.34 (gnomAD)
Structure: AlphaFold pLDDT 95.99

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

Similar variants

DERA p.Arg80Trp Uncertain significance ★ ⚠ same residue
DERA p.Ala115Ser Uncertain significance ★ ⚠ same type
DERA p.Ala131Thr Uncertain significance ★ ⚠ same type
DERA p.Ala228Gly Uncertain significance ★ ⚠ same type
DERA p.Ala262Val Uncertain significance ★ ⚠ same type
DERA p.Ala29Val Uncertain significance ★ ⚠ same type
DERA p.Arg105Gly Uncertain significance ★ ⚠ same type
DERA p.Arg105Trp 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/dera-p-arg80gly (accessed [today's date]).

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