Is DCD p.Gly46Val (c.137G>T) pathogenic?

DCD p.Gly46Val (c.137G>T) is classified Uncertain significance in DCD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.1557); Very rare (popmax 0.004%, afr).

How common is DCD p.Gly46Val (c.137G>T) in the general population?

DCD p.Gly46Val (c.137G>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about DCD p.Gly46Val (c.137G>T)?

AlphaMissense predicts likely benign (score 0.1557) — an in-silico prediction, not a clinical call.

DCD p.Gly46Val

c.137G>T · VCV4658696

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1557 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1557	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -6.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.29	GERP -0.63, phastCons 0.001
Regional constraint	o/e 1.04	unconstrained · MANE · 3,587 bp · p 0.63 · regional, not allelic
Overall
CADD	14.26	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.004% African / African-American · 3/74,922 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000929% 15/1,614,032 alleles · very rare exomes 8/1,461,842 · genomes 7/152,190 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,974
European (non-Finnish)	0.00102%	98,334

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: DCD
Protein: p.Gly46Val
Coding: c.137G>T
MANE Select: NM_053283
Type: single nucleotide variant
Location: chr12:54645668 (GRCh38)
Gene constraint: LOEUF 1.809 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.88 · 4 PDB
Residue 46: the 'disordered' region

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

Similar variants

DCD p.Asp71Asn Benign ★★ same type
DCD p.Asn32Lys Uncertain significance ★ ⚠ same type
DCD p.Asn32Ser Uncertain significance ★ ⚠ same type
DCD p.Asp101Glu Uncertain significance ★ ⚠ same type
DCD p.Glu89Lys Uncertain significance ★ ⚠ same type
DCD p.Glu92Gly Uncertain significance ★ ⚠ same type
DCD p.Gly81Arg Uncertain significance ★ ⚠ same type
DCD p.Leu65Phe 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/dcd-p-gly46val (accessed [today's date]).

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