Is DCDC1 p.Lys277Glu (c.829A>G) pathogenic?

DCDC1 p.Lys277Glu (c.829A>G) is classified Uncertain significance in DCDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-08). AlphaMissense: likely benign (0.1766); Ultra-rare (popmax 0.0165%, mid).

How common is DCDC1 p.Lys277Glu (c.829A>G) in the general population?

DCDC1 p.Lys277Glu (c.829A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about DCDC1 p.Lys277Glu (c.829A>G)?

AlphaMissense predicts likely benign (score 0.1766) — an in-silico prediction, not a clinical call.

DCDC1 p.Lys277Glu

c.829A>G · VCV3499999

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1766 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1766	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -6.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.57 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.4	GERP 0.56, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 450 kb · p 2.3e-08 · regional, not allelic
Overall
CADD	20.4	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 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00462% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00423%

Overall 0.00508% 82/1,613,536 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0096%	10,413
South Asian	0.00769%	13,005
European (non-Finnish)	0.00576%	17,347

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.Lys277Glu
Coding: c.829A>G
MANE Select: NM_001387274
Type: single nucleotide variant
Location: chr11:31290778 (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-lys277glu (accessed [today's date]).

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