Is DCSTAMP p.Cys74Phe (c.221G>T) pathogenic?

DCSTAMP p.Cys74Phe (c.221G>T) is classified Uncertain significance in DCSTAMP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.0718); Ultra-rare (popmax 0.0267%, amr).

How common is DCSTAMP p.Cys74Phe (c.221G>T) in the general population?

DCSTAMP p.Cys74Phe (c.221G>T) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

What do computational predictors say about DCSTAMP p.Cys74Phe (c.221G>T)?

AlphaMissense predicts likely benign (score 0.0718) — an in-silico prediction, not a clinical call.

DCSTAMP p.Cys74Phe

c.221G>T · rs771611522 · VCV2379404

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0718 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0718	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -3.89	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 3.4	GERP 0.78, phastCons 0.67
Regional constraint	o/e 0.95	unconstrained · MANE · 7,642 bp · p 0.28 · regional, not allelic
Overall
CADD	16.5	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

Grpmax group 0.0267% Admixed American · 16/60,004 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.0018% 29/1,614,054 alleles · ultra-rare exomes 27/1,461,890 · genomes 2/152,164 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,750
Remaining individualsnot grpmax-eligible	0.0032%	31,245
European (non-Finnish)	0.000932%	107,277

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: DCSTAMP
Protein: p.Cys74Phe
Coding: c.221G>T
MANE Select: NM_030788
dbSNP: rs771611522
Type: single nucleotide variant
Location: chr8:104348773 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.44

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

Similar variants

DCSTAMP p.Cys74Trp Uncertain significance ★ ⚠ same residue
DCSTAMP p.Asp349Gly Benign ★★ same type
DCSTAMP p.Arg259Thr Uncertain significance ★ ⚠ same type
DCSTAMP p.Arg92His Uncertain significance ★ ⚠ same type
DCSTAMP p.Asp349Glu Uncertain significance ★ ⚠ same type
DCSTAMP p.Asp468His Uncertain significance ★ ⚠ same type
DCSTAMP p.Gln185Arg Uncertain significance ★ ⚠ same type
DCSTAMP p.Gln345Pro 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/dcstamp-p-cys74phe (accessed [today's date]).

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