Is DRC11 p.Ala327Pro (c.979G>C) pathogenic?

DRC11 p.Ala327Pro (c.979G>C) is classified Likely benign in DRC11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-01). AlphaMissense: likely pathogenic (0.6636); Rare (popmax 0.632%, nfe).

How common is DRC11 p.Ala327Pro (c.979G>C) in the general population?

DRC11 p.Ala327Pro (c.979G>C) is rare (popmax 0.632%, nfe) (gnomAD).

What do computational predictors say about DRC11 p.Ala327Pro (c.979G>C)?

AlphaMissense predicts likely pathogenic (score 0.6636) — an in-silico prediction, not a clinical call.

DRC11 p.Ala327Pro

c.979G>C · rs191563773 · VCV2652036

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6636 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.632%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6636	likely pathogenic
REVEL	0.523	indeterminate
SaProt	LLR -5.17	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 1.4, phastCons 0.99
Regional constraint	o/e 0.96	unconstrained · MANE · 183 kb · p 0.19 · regional, not allelic
Overall
CADD	19.42	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 0.632% European (non-Finnish) · 7,274/1,150,850 alleles

Filtering AF 0.62% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.615%

Overall 0.511% 7,977/1,560,762 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.632%	158
Remaining individualsnot grpmax-eligible	0.529%	189
Ashkenazi Jewishnot grpmax-eligible	0.268%	373
Admixed American	0.231%	433
Middle Eastern	0.217%	461
Finnishnot grpmax-eligible	0.16%	626
African / African-American	0.0909%	1,100
South Asian	0.00827%	12,085
East Asian	0.00236%	42,330

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: DRC11
Protein: p.Ala327Pro
Coding: c.979G>C
MANE Select: NM_024726
dbSNP: rs191563773
Type: single nucleotide variant
Location: chr2:236441072 (GRCh38)
Structure: AlphaFold pLDDT 79.87 · 1 PDB

Full DRC11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRC11 p.Ala143Val Uncertain significance ★ ⚠ same type
DRC11 p.Ala574Pro Uncertain significance ★ ⚠ same type
DRC11 p.Ala594Val Uncertain significance ★ ⚠ same type
DRC11 p.Ala735Val Uncertain significance ★ ⚠ same type
DRC11 p.Ala804Gly Uncertain significance ★ ⚠ same type
DRC11 p.Ala806Val Uncertain significance ★ ⚠ same type
DRC11 p.Arg224His Uncertain significance ★ ⚠ same type
DRC11 p.Arg531Cys 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/drc11-p-ala327pro (accessed [today's date]).

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