Is DRC10 p.Ser387Pro (c.1159T>C) pathogenic?

DRC10 p.Ser387Pro (c.1159T>C) is classified Uncertain significance in DRC10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: likely pathogenic (0.8698); Very rare (popmax 0.00839%, nfe).

How common is DRC10 p.Ser387Pro (c.1159T>C) in the general population?

DRC10 p.Ser387Pro (c.1159T>C) is very rare (popmax 0.00839%, nfe) (gnomAD).

What do computational predictors say about DRC10 p.Ser387Pro (c.1159T>C)?

AlphaMissense predicts likely pathogenic (score 0.8698) — an in-silico prediction, not a clinical call.

DRC10 p.Ser387Pro

c.1159T>C · rs199910644 · VCV2516655

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8698 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00839%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8698	likely pathogenic · top 4% in DRC10
REVEL	0.104	moderately benign-leaning
SaProt	LLR -12.02	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP -4.2
Regional constraint	o/e 0.90	unconstrained · MANE · 13 kb · p 0.015 · regional, not allelic
Overall
CADD	8.882	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 0.00839% European (non-Finnish) · 99/1,179,944 alleles

Filtering AF 0.00702% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00652%

Overall 0.00645% 104/1,613,444 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00839%	11,919
Remaining individualsnot grpmax-eligible	0.0064%	15,618
Admixed American	0.00167%	59,952

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: DRC10
Protein: p.Ser387Pro
Coding: c.1159T>C
MANE Select: NM_001330452
dbSNP: rs199910644
Type: single nucleotide variant
Location: chr12:113195766 (GRCh38)
Structure: AlphaFold pLDDT 82.03 · 1 PDB

Full DRC10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRC10 p.Ala31Thr Uncertain significance ★ ⚠ same type
DRC10 p.Ala393Ser Uncertain significance ★ ⚠ same type
DRC10 p.Ala403Val Uncertain significance ★ ⚠ same type
DRC10 p.Ala404Thr Uncertain significance ★ ⚠ same type
DRC10 p.Ala59Val Uncertain significance ★ ⚠ same type
DRC10 p.Arg191Cys Uncertain significance ★ ⚠ same type
DRC10 p.Arg399Gly Uncertain significance ★ ⚠ same type
DRC10 p.Arg426Gln 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/drc10-p-ser387pro (accessed [today's date]).

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