Is DRC3 p.Ile55Val (c.163A>G) pathogenic?

DRC3 p.Ile55Val (c.163A>G) is classified Uncertain significance in DRC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: likely benign (0.2037); Very rare (popmax 0.00451%, nfe).

How common is DRC3 p.Ile55Val (c.163A>G) in the general population?

DRC3 p.Ile55Val (c.163A>G) is very rare (popmax 0.00451%, nfe) (gnomAD).

What do computational predictors say about DRC3 p.Ile55Val (c.163A>G)?

AlphaMissense predicts likely benign (score 0.2037) — an in-silico prediction, not a clinical call.

DRC3 p.Ile55Val

c.163A>G · rs1439176060 · VCV3085736

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2037 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00451%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2037	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -7.25	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Overall
CADD	23.1	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 0.00451% European (non-Finnish) · 53/1,176,180 alleles

Filtering AF 0.00351% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00319%

Overall 0.00348% 56/1,609,204 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00451%	22,192
Remaining individualsnot grpmax-eligible	0.00321%	31,128
Admixed American	0.00167%	59,824

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.Ile55Val
Coding: c.163A>G
MANE Select: NM_031294
dbSNP: rs1439176060
Type: single nucleotide variant
Location: chr17:17983830 (GRCh38)
Gene constraint: LOEUF 1.056 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.15 · 1 PDB

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

Similar variants

DRC3 p.Ala201Val Uncertain significance ★ ⚠ same type
DRC3 p.Ala221Thr Uncertain significance ★ ⚠ same type
DRC3 p.Ala228Val Uncertain significance ★ ⚠ same type
DRC3 p.Ala239Thr Uncertain significance ★ ⚠ same type
DRC3 p.Ala255Thr 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

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-ile55val (accessed [today's date]).

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