Is DCAKD p.Val110Met (c.328G>A) pathogenic?

DCAKD p.Val110Met (c.328G>A) is classified Uncertain significance in DCAKD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-14). AlphaMissense: likely pathogenic (0.6604); Ultra-rare (popmax 0.035%, amr).

How common is DCAKD p.Val110Met (c.328G>A) in the general population?

DCAKD p.Val110Met (c.328G>A) is ultra-rare (popmax 0.035%, amr) (gnomAD).

What do computational predictors say about DCAKD p.Val110Met (c.328G>A)?

AlphaMissense predicts likely pathogenic (score 0.6604) — an in-silico prediction, not a clinical call.

DCAKD p.Val110Met

c.328G>A · rs767182459 · VCV2509445

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6604 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6604	likely pathogenic
REVEL	0.39	indeterminate
SaProt	LLR -13.00	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 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 10 kb · p 0.24 · regional, not allelic
Overall
CADD	29.8	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 0.035% Admixed American · 21/59,998 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00452% 73/1,613,956 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.035%	2,857
South Asian	0.0209%	4,794
African / African-American	0.02%	4,994
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.00136%	73,747

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.Val110Met
Coding: c.328G>A
MANE Select: NM_001288655
dbSNP: rs767182459
Type: single nucleotide variant
Location: chr17:45030168 (GRCh38)
Gene constraint: LOEUF 1.164 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.62
Residue 110: 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 type
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-val110met (accessed [today's date]).

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