Is DCD p.Val99Ile (c.295G>A) pathogenic?

DCD p.Val99Ile (c.295G>A) is classified Likely benign in DCD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-10). AlphaMissense: likely benign (0.1016); Ultra-rare (popmax 0.0152%, amr).

How common is DCD p.Val99Ile (c.295G>A) in the general population?

DCD p.Val99Ile (c.295G>A) is ultra-rare (popmax 0.0152%, amr) (gnomAD).

What do computational predictors say about DCD p.Val99Ile (c.295G>A)?

AlphaMissense predicts likely benign (score 0.1016) — an in-silico prediction, not a clinical call.

DCD p.Val99Ile

c.295G>A · rs199541255 · VCV2331765

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1016 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0152%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1016	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -8.79	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 -0.25	GERP -2
Regional constraint	o/e 1.04	unconstrained · MANE · 3,587 bp · p 0.63 · regional, not allelic
Overall
CADD	0.317	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 0.0152% Admixed American · 9/59,210 alleles

Filtering AF 0.00793% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00585%

Overall 0.00318% 51/1,604,394 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0152%	6,579
Remaining individualsnot grpmax-eligible	0.0113%	8,883
East Asian	0.0112%	8,943
African / African-American	0.00407%	24,541
South Asian	0.00222%	45,029
European (non-Finnish)	0.00213%	47,022

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.Val99Ile
Coding: c.295G>A
MANE Select: NM_053283
dbSNP: rs199541255
Type: single nucleotide variant
Location: chr12:54644751 (GRCh38)
Gene constraint: LOEUF 1.809 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.88 · 4 PDB
Residue 99: an α-helix

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.Gly46Val Uncertain significance ★ ⚠ same type
DCD p.Gly81Arg 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-val99ile (accessed [today's date]).

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