Is DCAKD p.Arg80Gln (c.239G>A) pathogenic?

DCAKD p.Arg80Gln (c.239G>A) is classified Uncertain significance in DCAKD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-24). AlphaMissense: ambiguous (0.3685); Ultra-rare (popmax 0.04%, amr).

How common is DCAKD p.Arg80Gln (c.239G>A) in the general population?

DCAKD p.Arg80Gln (c.239G>A) is ultra-rare (popmax 0.04%, amr) (gnomAD).

What do computational predictors say about DCAKD p.Arg80Gln (c.239G>A)?

AlphaMissense predicts ambiguous (score 0.3685) — an in-silico prediction, not a clinical call.

DCAKD p.Arg80Gln

c.239G>A · rs776928993 · VCV2509778

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3685 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.04%, amr)

Computational evidence

Protein change
AlphaMissense	0.3685	ambiguous
REVEL	0.586	indeterminate
SaProt	LLR -10.58	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 10 kb · p 0.24 · regional, not allelic
Overall
CADD	32.0	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 0.04% Admixed American · 24/60,020 alleles

Filtering AF 0.0275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0234%

Overall 0.0183% 295/1,614,178 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.04%	2,501
European (non-Finnish)	0.0219%	4,574
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0096%	10,417
South Asian	0.00329%	30,361
African / African-American	0.00267%	37,520
Finnishnot grpmax-eligible	0.00156%	64,030

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: DCAKD
Protein: p.Arg80Gln
Coding: c.239G>A
MANE Select: NM_001288655
dbSNP: rs776928993
Type: single nucleotide variant
Location: chr17:45034264 (GRCh38)
Gene constraint: LOEUF 1.164 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.62
Residue 80: the dpck domain

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

Similar variants

DCAKD p.Arg80Trp Uncertain significance ★ ⚠ same residue
DCAKD p.Asp136Asn Uncertain significance ★★ ⚠ same type
DCAKD p.Ala214Thr Uncertain significance ★ ⚠ same type
DCAKD p.Ala214Val Uncertain significance ★ ⚠ same type
DCAKD p.Arg105Gln Uncertain significance ★ ⚠ same type
DCAKD p.Arg143Trp Uncertain significance ★ ⚠ same type
DCAKD p.Arg147Trp Uncertain significance ★ ⚠ same type
DCAKD p.Arg152Cys 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/dcakd-p-arg80gln (accessed [today's date]).

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