Is DCDC1 p.Val83Met (c.247G>A) pathogenic?

DCDC1 p.Val83Met (c.247G>A) is classified Benign in DCDC1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.122); Common (popmax 30.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with head and neck cancer.

What condition is associated with DCDC1 p.Val83Met (c.247G>A)?

DCDC1 p.Val83Met (c.247G>A) is associated with head and neck cancer (ClinVar).

What do computational predictors say about DCDC1 p.Val83Met (c.247G>A)?

AlphaMissense predicts likely benign (score 0.122) — an in-silico prediction, not a clinical call.

DCDC1 p.Val83Met

Q: How common is DCDC1 p.Val83Met (c.247G>A) in the general population?

DCDC1 p.Val83Met (c.247G>A) is common (popmax 30.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.247G>A · rs2761591 · VCV813015

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.122 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 30.1%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

head and neck cancer

Computational evidence

Protein change
AlphaMissense	0.122	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -7.44	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 1.2	GERP -1.5, phastCons 0.99
Regional constraint	o/e 1.13	unconstrained · MANE · 450 kb · p 2.3e-08 · regional, not allelic
Overall
CADD	16.98	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 30.1% African / African-American · 22,581/74,924 alleles

Filtering AF 29.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 29.7%

Overall 2.41% 38,951/1,613,944 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	30.1%	3
Admixed American	16.4%	6
Remaining individualsnot grpmax-eligible	3.15%	32
Middle Eastern	2.72%	37
East Asian	1.93%	52
South Asian	0.584%	171
Ashkenazi Jewishnot grpmax-eligible	0.318%	315
European (non-Finnish)	0.244%	410
Finnishnot grpmax-eligible	0.00937%	10,668

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.Val83Met
Coding: c.247G>A
MANE Select: NM_001387274
dbSNP: rs2761591
Type: single nucleotide variant
Location: chr11:31307826 (GRCh38)
Gene constraint: LOEUF 1.093 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.53
Residue 83: a UniProt-annotated variant site (in)

Full DCDC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

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-val83met (accessed [today's date]).

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