Is DRC9 p.Met111Val (c.331A>G) pathogenic?

DRC9 p.Met111Val (c.331A>G) is classified Likely benign in DRC9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: likely benign (0.0567); Ultra-rare (popmax 0.0276%, nfe).

How common is DRC9 p.Met111Val (c.331A>G) in the general population?

DRC9 p.Met111Val (c.331A>G) is ultra-rare (popmax 0.0276%, nfe) (gnomAD).

What do computational predictors say about DRC9 p.Met111Val (c.331A>G)?

AlphaMissense predicts likely benign (score 0.0567) — an in-silico prediction, not a clinical call.

DRC9 p.Met111Val

c.331A>G · rs149674426 · VCV2456344

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0567 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0276%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0567	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -5.11	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 -3.2
Regional constraint	o/e 0.94	unconstrained · MANE · 56 kb · p 0.19 · regional, not allelic
Overall
CADD	0.004	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 0.0276% European (non-Finnish) · 326/1,179,932 alleles

Filtering AF 0.0251% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0241%

Overall 0.0227% 367/1,613,962 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0276%	3,619
South Asian	0.0263%	3,795
Admixed American	0.01%	9,999
Remaining individualsnot grpmax-eligible	0.0096%	10,413
African / African-American	0.004%	24,977
East Asian	0.00223%	44,904
Finnishnot grpmax-eligible	0.00156%	64,044

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.Met111Val
Coding: c.331A>G
MANE Select: NM_032263
dbSNP: rs149674426
Type: single nucleotide variant
Location: chr3:197938732 (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.Ter111= 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-met111val (accessed [today's date]).

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