Is DCC p.Ala455Val (c.1364C>T) pathogenic?

DCC p.Ala455Val (c.1364C>T) is classified Likely benign in DCC (ClinVar, No assertion criteria, 2 submitters; last evaluated 2022-09-07). AlphaMissense: likely benign (0.2084); Rare (popmax 0.304%, afr); Associated with DCC-related disorder.

What condition is associated with DCC p.Ala455Val (c.1364C>T)?

DCC p.Ala455Val (c.1364C>T) is associated with DCC-related disorder (ClinVar).

How common is DCC p.Ala455Val (c.1364C>T) in the general population?

DCC p.Ala455Val (c.1364C>T) is rare (popmax 0.304%, afr) (gnomAD).

What do computational predictors say about DCC p.Ala455Val (c.1364C>T)?

AlphaMissense predicts likely benign (score 0.2084) — an in-silico prediction, not a clinical call.

DCC p.Ala455Val

c.1364C>T · rs145985306 · VCV3034874

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2084 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.304%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DCC-related disorder

Computational evidence

Protein change
AlphaMissense	0.2084	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -8.20	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 2.3	GERP 0.96, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,190 kb · p 0.4 · regional, not allelic
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

Grpmax group 0.304% African / African-American · 228/74,902 alleles

Filtering AF 0.272% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.259%

Overall 0.0183% 295/1,613,952 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.304%	329
Remaining individualsnot grpmax-eligible	0.0128%	7,811
Admixed American	0.00833%	11,998
Finnishnot grpmax-eligible	0.00781%	12,802
South Asian	0.00769%	13,010
European (non-Finnish)	0.00347%	28,781
East Asian	0.00223%	44,884

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: DCC
Protein: p.Ala455Val
Coding: c.1364C>T
MANE Select: NM_005215
dbSNP: rs145985306
Type: single nucleotide variant
Location: chr18:53157458 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 455: a UniProt-annotated variant site (in mrmv1; likely pathogenic); the fibronectin type-iii 1 domain

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

Disease context

DCC-related disorder

Similar variants

DCC c.2828-1G>A Likely pathogenic ★ same condition
DCC c.3898+2T>C Likely pathogenic ★ same condition
DCC p.Arg501Ter Likely pathogenic ★ same condition
DCC p.Glu512Ter Likely pathogenic ★ same condition
DCC p.Trp508Ter Likely pathogenic ★ same condition
DCC p.Trp745Ter Likely pathogenic ★ same condition
DCC p.Pro1086Leu Uncertain significance ⚠ same condition
DCC p.Thr614Ile Uncertain significance ⚠ 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/dcc-p-ala455val (accessed [today's date]).

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