Is DRC9 p.Val94Met (c.280G>A) pathogenic?

DRC9 p.Val94Met (c.280G>A) is classified Likely benign in DRC9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-19). AlphaMissense: likely benign (0.0689); Very rare (popmax 0.00958%, nfe).

How common is DRC9 p.Val94Met (c.280G>A) in the general population?

DRC9 p.Val94Met (c.280G>A) is very rare (popmax 0.00958%, nfe) (gnomAD).

What do computational predictors say about DRC9 p.Val94Met (c.280G>A)?

AlphaMissense predicts likely benign (score 0.0689) — an in-silico prediction, not a clinical call.

DRC9 p.Val94Met

c.280G>A · rs146833269 · VCV2515273

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0689 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00958%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0689	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -7.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.44	donor gain · deltas
Constraint at this position
Conservation	phyloP -5.1
Regional constraint	o/e 0.94	unconstrained · MANE · 56 kb · p 0.19 · regional, not allelic
Overall
CADD	0.022	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 0.00958% European (non-Finnish) · 113/1,179,860 alleles

Filtering AF 0.00809% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0076%

Overall 0.00756% 122/1,613,820 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00958%	10,441
African / African-American	0.00667%	14,983
Remaining individualsnot grpmax-eligible	0.0032%	31,237
East Asian	0.00223%	44,896
Admixed American	0.00167%	59,976

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: DRC9
Protein: p.Val94Met
Coding: c.280G>A
MANE Select: NM_032263
dbSNP: rs146833269
Type: single nucleotide variant
Location: chr3:197943780 (GRCh38)
Structure: AlphaFold pLDDT 72.42 · 3 PDB

Full DRC9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RPL35A p.Ala94= Benign/Likely benign ★★ same residue
RPL35A c.309+3G>C Uncertain significance ★★ same type
RPL35A c.309+4A>T Uncertain significance ★★ same type
RPL35A p.Ala12Thr Uncertain significance ★★ ⚠ same type
RPL35A p.Ala12Val Uncertain significance ★★ ⚠ same type
RPL35A p.Arg19Trp Uncertain significance ★★ ⚠ same type
RPL35A p.Arg46= Uncertain significance ★★ same type
RPL35A p.Arg76Gln 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/drc9-p-val94met (accessed [today's date]).

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