Is DCC p.Ser124Phe (c.371C>T) pathogenic?

DCC p.Ser124Phe (c.371C>T) is classified Uncertain significance in DCC (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-09). AlphaMissense: likely benign (0.3028); Absent from gnomAD v4.1; Associated with colorectal cancer.

What condition is associated with DCC p.Ser124Phe (c.371C>T)?

DCC p.Ser124Phe (c.371C>T) is associated with colorectal cancer (ClinVar).

How common is DCC p.Ser124Phe (c.371C>T) in the general population?

DCC p.Ser124Phe (c.371C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCC p.Ser124Phe (c.371C>T)?

AlphaMissense predicts likely benign (score 0.3028) — an in-silico prediction, not a clinical call.

DCC p.Ser124Phe

c.371C>T · rs2037008530 · VCV1030892

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3028 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

colorectal cancer

Computational evidence

Protein change
AlphaMissense	0.3028	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -3.46	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 5	GERP 0.23, phastCons 0.59
Regional constraint	o/e 0.98	unconstrained · MANE · 1,190 kb · p 0.4 · regional, not allelic
Overall
CADD	25.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DCC
Protein: p.Ser124Phe
Coding: c.371C>T
MANE Select: NM_005215
dbSNP: rs2037008530
Type: single nucleotide variant
Location: chr18:52752333 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 124: the ig-like c2-type 1 domain

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

Disease context

colorectal cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DCC c.2053+9T>C Benign/Likely benign ★★ same condition
DCC c.91+7G>A Benign ★★ same condition
DCC p.Leu720= Benign/Likely benign ★★ same condition
DCC p.Val354= Benign/Likely benign ★★ same condition
DCC p.Arg1343His Likely benign ★ same condition
DCC p.Arg1291Gln Uncertain significance ⚠ same condition
DCC p.Asn316fs Pathogenic same condition
DCC p.Arg1021Ter Pathogenic ★★ 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/dcc-p-ser124phe (accessed [today's date]).

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