Is DRC9 p.Ser200Ile (c.599G>T) pathogenic?

DRC9 p.Ser200Ile (c.599G>T) is classified Uncertain significance in DRC9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely benign (0.1219); Very rare (popmax 0.00288%, nfe).

How common is DRC9 p.Ser200Ile (c.599G>T) in the general population?

DRC9 p.Ser200Ile (c.599G>T) is very rare (popmax 0.00288%, nfe) (gnomAD).

What do computational predictors say about DRC9 p.Ser200Ile (c.599G>T)?

AlphaMissense predicts likely benign (score 0.1219) — an in-silico prediction, not a clinical call.

DRC9 p.Ser200Ile

c.599G>T · rs1278317901 · VCV3110461

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1219 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00288%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1219	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -5.48	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 -3.6
Regional constraint	o/e 0.94	unconstrained · MANE · 56 kb · p 0.19 · regional, not allelic
Overall
CADD	7.05	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 0.00288% European (non-Finnish) · 34/1,179,638 alleles

Filtering AF 0.00208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00217% 35/1,613,416 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00288%	34,695
Remaining individualsnot grpmax-eligible	0.0016%	62,442

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.Ser200Ile
Coding: c.599G>T
MANE Select: NM_032263
dbSNP: rs1278317901
Type: single nucleotide variant
Location: chr3:197932219 (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 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
RPL35A p.Arg85Gly 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-ser200ile (accessed [today's date]).

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