Is DCDC1 p.Thr486Met (c.1457C>T) pathogenic?

DCDC1 p.Thr486Met (c.1457C>T) is classified Benign in DCDC1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-07). AlphaMissense: likely benign (0.0906); Low-frequency (popmax 2.83%, afr); Associated with DCDC1-related disorder.

What condition is associated with DCDC1 p.Thr486Met (c.1457C>T)?

DCDC1 p.Thr486Met (c.1457C>T) is associated with DCDC1-related disorder (ClinVar).

How common is DCDC1 p.Thr486Met (c.1457C>T) in the general population?

DCDC1 p.Thr486Met (c.1457C>T) is low-frequency (popmax 2.83%, afr) (gnomAD).

What do computational predictors say about DCDC1 p.Thr486Met (c.1457C>T)?

AlphaMissense predicts likely benign (score 0.0906) — an in-silico prediction, not a clinical call.

DCDC1 p.Thr486Met

c.1457C>T · rs75249430 · VCV3044067

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0906 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.83%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

DCDC1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0906	likely benign
SaProt	LLR -7.32	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.29, phastCons 0.99
Regional constraint	o/e 1.13	unconstrained · MANE · 450 kb · p 2.3e-08 · regional, not allelic
Overall
CADD	16.09	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 2.83% African / African-American · 1,622/57,304 alleles

Filtering AF 2.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.67%

Overall 0.265% 1,859/702,568 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.83%	35
Remaining individualsnot grpmax-eligible	0.303%	330
Admixed American	0.166%	602
Middle Eastern	0.0688%	1,454
South Asian	0.0133%	7,509
European (non-Finnish)	0.0107%	9,383
East Asian	0.00268%	37,270
Finnishnot grpmax-eligible	0.00226%	44,234

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.Thr486Met
Coding: c.1457C>T
MANE Select: NM_001387274
dbSNP: rs75249430
Type: single nucleotide variant
Location: chr11:31127497 (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

Disease context

DCDC1-related disorder

Similar variants

DCDC1 p.Cys1699Ter Likely pathogenic ★ same condition
DCDC1 c.164+3A>G Likely benign same condition
DCDC1 c.1983+10T>C Likely benign same condition
DCDC1 c.2298+8C>T Benign same condition
DCDC1 c.2716-10C>A Benign same condition
DCDC1 c.5233+7A>G Likely benign same condition
DCDC1 p.Ala684= Likely benign same condition
DCDC1 p.Ala731= Likely benign same condition

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-thr486met (accessed [today's date]).

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