Is DOC2A p.Pro392Ala (c.1174C>G) pathogenic?

DOC2A p.Pro392Ala (c.1174C>G) is classified Benign in DOC2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0484); Low-frequency (popmax 1.2%, nfe).

How common is DOC2A p.Pro392Ala (c.1174C>G) in the general population?

DOC2A p.Pro392Ala (c.1174C>G) is low-frequency (popmax 1.2%, nfe) (gnomAD).

What do computational predictors say about DOC2A p.Pro392Ala (c.1174C>G)?

AlphaMissense predicts likely benign (score 0.0484) — an in-silico prediction, not a clinical call.

DOC2A p.Pro392Ala

c.1174C>G · rs202062683 · VCV770252

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0484 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.2%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0484	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -5.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 0.36, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 4,033 bp · p 0.00084 · regional, not allelic
Overall
CADD	8.398	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 1.2% European (non-Finnish) · 14,044/1,168,894 alleles

Filtering AF 1.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.18%

Overall 0.954% 15,148/1,588,566 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.2%	83
Remaining individualsnot grpmax-eligible	0.954%	105
Admixed American	0.363%	276
African / African-American	0.202%	495
Ashkenazi Jewishnot grpmax-eligible	0.141%	709
Middle Eastern	0.134%	744
Finnishnot grpmax-eligible	0.0951%	1,052
South Asian	0.0669%	1,495
East Asian	0.00228%	43,764

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: DOC2A
Protein: p.Pro392Ala
Coding: c.1174C>G
MANE Select: NM_003586
dbSNP: rs202062683
Type: single nucleotide variant
Location: chr16:30006215 (GRCh38)
Gene constraint: LOEUF 0.974 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.55 · 1 PDB
Residue 392: the 'interaction with unc13d' region

Full DOC2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOC2A c.715-4G>A Benign ★★ same type
DOC2A p.Gly48Ser Benign ★★ same type
DOC2A p.Pro376Leu Benign ★★ same type
DOC2A p.Ala125Thr Uncertain significance ★ ⚠ same type
DOC2A p.Ala227Val Uncertain significance ★ ⚠ same type
DOC2A p.Ala228Val Uncertain significance ★ ⚠ same type
DOC2A p.Ala242Val Uncertain significance ★ ⚠ same type
DOC2A p.Ala332Thr 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/doc2a-p-pro392ala (accessed [today's date]).

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