Is DOC2B p.Phe40Leu (c.118T>C) pathogenic?

DOC2B p.Phe40Leu (c.118T>C) is classified Uncertain significance in DOC2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely pathogenic (0.8861); Absent from gnomAD v4.1.

How common is DOC2B p.Phe40Leu (c.118T>C) in the general population?

DOC2B p.Phe40Leu (c.118T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOC2B p.Phe40Leu (c.118T>C)?

AlphaMissense predicts likely pathogenic (score 0.8861) — an in-silico prediction, not a clinical call.

DOC2B p.Phe40Leu

c.118T>C · VCV3504309

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8861 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,128,376)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8861	likely pathogenic
REVEL	0.148	moderately benign-leaning
SaProt	LLR -4.62	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 6.9	phastCons 1
Overall
CADD	20.5	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

No allele count reported in gnomAD v4.1 (AN 1,128,376). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DOC2B
Protein: p.Phe40Leu
Coding: c.118T>C
MANE Select: NM_003585
Type: single nucleotide variant
Location: chr17:181362 (GRCh38)
Gene constraint: LOEUF 1.371 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.21
Residue 40: the 'mediates interaction with dynlt1' region; the 'disordered' region

Full DOC2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOC2B p.Ala103Thr Uncertain significance ★ ⚠ same type
DOC2B p.Ala295Thr Uncertain significance ★ ⚠ same type
DOC2B p.Ala54Glu Uncertain significance ★ ⚠ same type
DOC2B p.Ala58Ser Uncertain significance ★ ⚠ same type
DOC2B p.Ala63Thr Uncertain significance ★ ⚠ same type
DOC2B p.Arg186Cys Uncertain significance ★ same type
DOC2B p.Arg186His Uncertain significance ★ ⚠ same type
DOC2B p.Arg209His 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/doc2b-p-phe40leu (accessed [today's date]).

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