Is DCAKD p.Arg80Trp (c.238C>T) pathogenic?

DCAKD p.Arg80Trp (c.238C>T) is classified Uncertain significance in DCAKD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-21). AlphaMissense: likely pathogenic (0.5834); Ultra-rare (popmax 0.0164%, mid).

How common is DCAKD p.Arg80Trp (c.238C>T) in the general population?

DCAKD p.Arg80Trp (c.238C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about DCAKD p.Arg80Trp (c.238C>T)?

AlphaMissense predicts likely pathogenic (score 0.5834) — an in-silico prediction, not a clinical call.

DCAKD p.Arg80Trp

c.238C>T · rs200330941 · VCV2387900

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5834 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5834	likely pathogenic
REVEL	0.545	indeterminate
SaProt	LLR -14.66	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 10 kb · p 0.24 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00545% 88/1,614,038 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.145%	689
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.00768%	13,013
Admixed American	0.00333%	30,000
Remaining individualsnot grpmax-eligible	0.0032%	31,240
European (non-Finnish)	0.0028%	35,759

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg80Trp
Coding: c.238C>T
MANE Select: NM_001288655
dbSNP: rs200330941
Type: single nucleotide variant
Location: chr17:45034265 (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.Arg80Gln 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-arg80trp (accessed [today's date]).

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