Is DCAKD p.Val39Met (c.115G>A) pathogenic?

DCAKD p.Val39Met (c.115G>A) is classified Uncertain significance in DCAKD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-25). AlphaMissense: ambiguous (0.4803); Very rare (popmax 0.00881%, nfe).

How common is DCAKD p.Val39Met (c.115G>A) in the general population?

DCAKD p.Val39Met (c.115G>A) is very rare (popmax 0.00881%, nfe) (gnomAD).

What do computational predictors say about DCAKD p.Val39Met (c.115G>A)?

AlphaMissense predicts ambiguous (score 0.4803) — an in-silico prediction, not a clinical call.

DCAKD p.Val39Met

c.115G>A · VCV3499955

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4803 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00881%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4803	ambiguous
REVEL	0.296	indeterminate
SaProt	LLR -8.60	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 10 kb · p 0.24 · regional, not allelic
Overall
CADD	25.8	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 0.00881% European (non-Finnish) · 104/1,179,994 alleles

Filtering AF 0.00741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00692%

Overall 0.00793% 128/1,613,650 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0252%	3,973
European (non-Finnish)grpmax	0.00881%	11,346
Remaining individualsnot grpmax-eligible	0.0064%	15,624
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Admixed American	0.00333%	30,005
African / African-American	0.00133%	75,050

Finnish 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.Val39Met
Coding: c.115G>A
MANE Select: NM_001288655
Type: single nucleotide variant
Location: chr17:45034388 (GRCh38)
Gene constraint: LOEUF 1.164 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.62
Residue 39: 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-val39met (accessed [today's date]).

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