Is DRC3 p.Ala201Val (c.602C>T) pathogenic?

DRC3 p.Ala201Val (c.602C>T) is classified Uncertain significance in DRC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). AlphaMissense: likely benign (0.3193); Very rare (popmax 0.00784%, amr).

How common is DRC3 p.Ala201Val (c.602C>T) in the general population?

DRC3 p.Ala201Val (c.602C>T) is very rare (popmax 0.00784%, amr) (gnomAD).

What do computational predictors say about DRC3 p.Ala201Val (c.602C>T)?

AlphaMissense predicts likely benign (score 0.3193) — an in-silico prediction, not a clinical call.

DRC3 p.Ala201Val

c.602C>T · VCV4014805

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3193 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00784%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3193	likely benign
REVEL	0.205	benign-leaning
SaProt	LLR -13.42	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.5, phastCons 1
Overall
CADD	26.2	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 0.00784% Admixed American · 4/51,006 alleles

Filtering AF 0.00388% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00354%

Overall 0.00477% 74/1,552,140 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00784%	12,752
South Asian	0.00714%	14,013
Remaining individualsnot grpmax-eligible	0.00664%	15,051
European (non-Finnish)	0.00497%	20,129
Ashkenazi Jewishnot grpmax-eligible	0.00349%	28,640
Finnishnot grpmax-eligible	0.00167%	59,970
African / African-American	0.00137%	73,028

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: DRC3
Protein: p.Ala201Val
Coding: c.602C>T
MANE Select: NM_133180 · reported on NM_031294
Type: single nucleotide variant
Location: chr17:17994309 (GRCh38)
Structure: AlphaFold pLDDT 75.86 · 2 PDB
Residue 201: the 'disordered' region

Full DRC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRC3 p.Ala221Thr Uncertain significance ★ ⚠ same type
DRC3 p.Ala228Val Uncertain significance ★ ⚠ same type
DRC3 p.Ala239Thr Uncertain significance ★ ⚠ same type
DRC3 p.Arg120Gln Uncertain significance ★ ⚠ same type
DRC3 p.Arg142Trp Uncertain significance ★ ⚠ same type
DRC3 p.Arg191Gln Uncertain significance ★ ⚠ same type
DRC3 p.Arg192Cys Uncertain significance ★ ⚠ same type
DRC3 p.Arg192His 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/drc3-p-ala201val (accessed [today's date]).

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