Is DSC1 p.Phe822Val (c.2464T>G) pathogenic?

DSC1 p.Phe822Val (c.2464T>G) is classified Uncertain significance in DSC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: ambiguous (0.5585); Very rare (popmax 0.00764%, nfe).

How common is DSC1 p.Phe822Val (c.2464T>G) in the general population?

DSC1 p.Phe822Val (c.2464T>G) is very rare (popmax 0.00764%, nfe) (gnomAD).

What do computational predictors say about DSC1 p.Phe822Val (c.2464T>G)?

AlphaMissense predicts ambiguous (score 0.5585) — an in-silico prediction, not a clinical call.

DSC1 p.Phe822Val

c.2464T>G · VCV4662206

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5585 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00764%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5585	ambiguous
REVEL	0.569	indeterminate
SaProt	LLR -6.15	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.9, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 32 kb · p 0.23 · regional, not allelic
Overall
CADD	26.5	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 0.00764% European (non-Finnish) · 90/1,178,304 alleles

Filtering AF 0.00632% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00585%

Overall 0.00651% 95/1,459,904 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00764%	13,092
Remaining individualsnot grpmax-eligible	0.0032%	31,211
African / African-American	0.00267%	37,489
South Asian	0.0011%	91,036

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: DSC1
Protein: p.Phe822Val
Coding: c.2464T>G
MANE Select: NM_024421
Type: single nucleotide variant
Location: chr18:31131617 (GRCh38)
Gene constraint: LOEUF 0.951 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.16 · 1 PDB

Full DSC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DSC1 p.Phe822Cys Uncertain significance ★ ⚠ same residue
DSC1 p.Ile200Thr Benign ★★ ⚠ same type
DSC1 p.Met659Arg Benign ★★ same type
DSC1 p.Thr710= Benign ★★ same type
DSC1 p.Ala128Pro Uncertain significance ★ ⚠ same type
DSC1 p.Ala209Val Uncertain significance ★ ⚠ same type
DSC1 p.Ala221Glu Uncertain significance ★ ⚠ same type
DSC1 p.Ala239Thr 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/dsc1-p-phe822val (accessed [today's date]).

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