Is DOP1A p.Pro787Ser (c.2359C>T) pathogenic?

DOP1A p.Pro787Ser (c.2359C>T) is classified Uncertain significance in DOP1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-14). AlphaMissense: likely pathogenic (0.651); Ultra-rare (popmax 0.0183%, amr).

How common is DOP1A p.Pro787Ser (c.2359C>T) in the general population?

DOP1A p.Pro787Ser (c.2359C>T) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

What do computational predictors say about DOP1A p.Pro787Ser (c.2359C>T)?

AlphaMissense predicts likely pathogenic (score 0.651) — an in-silico prediction, not a clinical call.

DOP1A p.Pro787Ser

c.2359C>T · VCV3504730

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.651 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.651	likely pathogenic
REVEL	0.173	moderately benign-leaning
SaProt	LLR -6.02	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 8,790 bp · p 0.00027 · regional, not allelic
Overall
CADD	24.8	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 0.0183% Admixed American · 11/59,986 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.000682% 11/1,613,684 alleles · ultra-rare exomes 8/1,461,510 · genomes 3/152,174 · joint denominator

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: DOP1A
Protein: p.Pro787Ser
Coding: c.2359C>T
MANE Select: NM_015018
Type: single nucleotide variant
Location: chr6:83130140 (GRCh38)
Gene constraint: LOEUF 0.395 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.63

Full DOP1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PGM3 p.Arg492Ter Pathogenic/Likely pathogenic ★★ same type
PGM3 p.Ala531Val Uncertain significance ★★ ⚠ same type
PGM3 p.Arg505Gln Uncertain significance ★★ ⚠ same type
PGM3 p.Glu479Gln Uncertain significance ★★ ⚠ same type
PGM3 p.Ile534Thr Uncertain significance ★★ ⚠ same type
PGM3 p.Pro538Thr Uncertain significance ★★ ⚠ same type
PGM3 p.Val461Leu Uncertain significance ★★ ⚠ same type
PGM3 p.Val504Ile 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/dop1a-p-pro787ser (accessed [today's date]).

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