Is DRC5 p.Pro307Gln (c.920C>A) pathogenic?

DRC5 p.Pro307Gln (c.920C>A) is classified Uncertain significance in DRC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-09). AlphaMissense: likely benign (0.3263); Ultra-rare (popmax 0.0867%, afr).

How common is DRC5 p.Pro307Gln (c.920C>A) in the general population?

DRC5 p.Pro307Gln (c.920C>A) is ultra-rare (popmax 0.0867%, afr) (gnomAD).

What do computational predictors say about DRC5 p.Pro307Gln (c.920C>A)?

AlphaMissense predicts likely benign (score 0.3263) — an in-silico prediction, not a clinical call.

DRC5 p.Pro307Gln

c.920C>A · rs150111506 · VCV2344843

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3263 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0867%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3263	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -11.21	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 7,641 bp · p 0.39 · regional, not allelic
Overall
CADD	26.1	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 0.0867% African / African-American · 65/74,940 alleles

Filtering AF 0.0698% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0636%

Overall 0.00429% 69/1,610,236 alleles · ultra-rare exomes 37/1,457,998 · genomes 32/152,238 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0867%	1,153
Admixed American	0.00333%	30,006
Remaining individualsnot grpmax-eligible	0.0032%	31,230

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: DRC5
Protein: p.Pro307Gln
Coding: c.920C>A
MANE Select: NM_182539
dbSNP: rs150111506
Type: single nucleotide variant
Location: chr6:44282486 (GRCh38)
Structure: AlphaFold pLDDT 83.02 · 1 PDB

Full DRC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRC5 p.Ala351Asp Uncertain significance ★ ⚠ same type
DRC5 p.Ala381Thr Uncertain significance ★ ⚠ same type
DRC5 p.Ala385Gly Uncertain significance ★ ⚠ same type
DRC5 p.Arg133His Uncertain significance ★ ⚠ same type
DRC5 p.Arg133Pro Uncertain significance ★ ⚠ same type
DRC5 p.Arg158Gln Uncertain significance ★ ⚠ same type
DRC5 p.Arg185Gly Uncertain significance ★ ⚠ same type
DRC5 p.Arg185Trp 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/drc5-p-pro307gln (accessed [today's date]).

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