Is DCST2 p.Phe473Ser (c.1418T>C) pathogenic?

DCST2 p.Phe473Ser (c.1418T>C) is classified Uncertain significance in DCST2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-28). AlphaMissense: likely pathogenic (0.7972); Very rare (popmax 0.00576%, nfe).

How common is DCST2 p.Phe473Ser (c.1418T>C) in the general population?

DCST2 p.Phe473Ser (c.1418T>C) is very rare (popmax 0.00576%, nfe) (gnomAD).

What do computational predictors say about DCST2 p.Phe473Ser (c.1418T>C)?

AlphaMissense predicts likely pathogenic (score 0.7972) — an in-silico prediction, not a clinical call.

DCST2 p.Phe473Ser

c.1418T>C · rs750278151 · VCV2214982

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7972 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00576%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7972	likely pathogenic · top 9% in DCST2
REVEL	0.433	indeterminate
SaProt	LLR -7.93	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.075 · regional, not allelic
Overall
CADD	24.7	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 0.00576% European (non-Finnish) · 68/1,180,038 alleles

Filtering AF 0.00462% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00422%

Overall 0.00446% 72/1,614,092 alleles · very rare exomes 69/1,461,874 · genomes 3/152,218 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00576%	17,353
Remaining individualsnot grpmax-eligible	0.0048%	20,829
African / African-American	0.00133%	74,942

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: DCST2
Protein: p.Phe473Ser
Coding: c.1418T>C
MANE Select: NM_144622
dbSNP: rs750278151
Type: single nucleotide variant
Location: chr1:155026640 (GRCh38)
Gene constraint: LOEUF 0.941 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.49

Full DCST2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCST2 p.Ala135Thr Uncertain significance ★ ⚠ same type
DCST2 p.Ala141Thr Uncertain significance ★ ⚠ same type
DCST2 p.Ala20Thr Uncertain significance ★ ⚠ same type
DCST2 p.Ala341Val Uncertain significance ★ ⚠ same type
DCST2 p.Ala39Thr Uncertain significance ★ ⚠ same type
DCST2 p.Ala597Asp Uncertain significance ★ ⚠ same type
DCST2 p.Ala668Val Uncertain significance ★ ⚠ same type
DCST2 p.Ala670Val 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/dcst2-p-phe473ser (accessed [today's date]).

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