Is DCC p.Lys315Thr (c.944A>C) pathogenic?

DCC p.Lys315Thr (c.944A>C) is classified Benign in DCC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: ambiguous (0.5046); Low-frequency (popmax 1.41%, sas).

How common is DCC p.Lys315Thr (c.944A>C) in the general population?

DCC p.Lys315Thr (c.944A>C) is low-frequency (popmax 1.41%, sas) (gnomAD).

What do computational predictors say about DCC p.Lys315Thr (c.944A>C)?

AlphaMissense predicts ambiguous (score 0.5046) — an in-silico prediction, not a clinical call.

DCC p.Lys315Thr

c.944A>C · rs145827180 · VCV723447

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5046 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.41%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5046	ambiguous
REVEL	0.135	moderately benign-leaning
SaProt	LLR -6.92	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 2.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,190 kb · p 0.4 · regional, not allelic
Overall
CADD	23.5	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 1.41% South Asian · 1,282/91,066 alleles

Filtering AF 1.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.32%

Overall 0.0842% 1,358/1,612,678 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.41%	71
Remaining individualsnot grpmax-eligible	0.103%	975
Middle Eastern	0.033%	3,026
African / African-American	0.00534%	18,742
Admixed American	0.00334%	29,959
European (non-Finnish)	0.000339%	294,735

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.Lys315Thr
Coding: c.944A>C
MANE Select: NM_005215
dbSNP: rs145827180
Type: single nucleotide variant
Location: chr18:52925329 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 315: a UniProt-annotated variant site (in mrmv1; likely pathogenic); the ig-like c2-type 3 domain

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

Similar variants

DCC p.Arg1021Ter Pathogenic ★★ same type
DCC p.Arg1025Ter Pathogenic/Likely pathogenic ★★ same type
DCC p.Arg275Ter Pathogenic ★★ same type
DCC p.Arg879Ter Pathogenic/Likely pathogenic ★★ same type
DCC c.3620-2A>G Uncertain significance ★★ same type
DCC p.Arg597Gln Uncertain significance ★★ ⚠ same type
DCC p.Gly1294Arg Uncertain significance ★★ ⚠ same type
DCC p.Gly55Arg Uncertain significance ★★ ⚠ 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-lys315thr (accessed [today's date]).

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