Is DCDC1 p.Leu282Phe (c.844C>T) pathogenic?

DCDC1 p.Leu282Phe (c.844C>T) is classified Uncertain significance in DCDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-10). AlphaMissense: likely benign (0.2206); Very rare (popmax 0.00892%, eas).

How common is DCDC1 p.Leu282Phe (c.844C>T) in the general population?

DCDC1 p.Leu282Phe (c.844C>T) is very rare (popmax 0.00892%, eas) (gnomAD).

What do computational predictors say about DCDC1 p.Leu282Phe (c.844C>T)?

AlphaMissense predicts likely benign (score 0.2206) — an in-silico prediction, not a clinical call.

DCDC1 p.Leu282Phe

c.844C>T · rs377121072 · VCV3080423

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2206 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2206	likely benign
REVEL	0.459	indeterminate
SaProt	LLR -7.27	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.4	GERP 1.2, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 450 kb · p 2.3e-08 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,850 alleles

Filtering AF 0.00605% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00565%

Overall 0.00632% 102/1,613,320 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0128%	7,807
East Asiangrpmax	0.00892%	11,212
European (non-Finnish)	0.00738%	13,558
Finnishnot grpmax-eligible	0.00313%	31,997
African / African-American	0.00134%	74,896

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DCDC1
Protein: p.Leu282Phe
Coding: c.844C>T
MANE Select: NM_001387274
dbSNP: rs377121072
Type: single nucleotide variant
Location: chr11:31290763 (GRCh38)
Gene constraint: LOEUF 1.093 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.53

Full DCDC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCDC1 p.Gln95His Uncertain significance ★★ ⚠ same type
DCDC1 p.Thr239Met Uncertain significance ★★ ⚠ same type
DCDC1 p.Thr317Ala Uncertain significance ★★ ⚠ same type
DCDC1 c.591+13C>T Benign ★★ same type
DCDC1 p.Ala1431Thr Benign ★★ ⚠ same type
DCDC1 p.Glu200= Benign ★★ same type
DCDC1 p.Leu224= Benign ★★ same type
DCDC1 p.Lys1494Arg Benign ★★ 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/dcdc1-p-leu282phe (accessed [today's date]).

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