Is DCST2 p.Val248Ile (c.742G>A) pathogenic?

DCST2 p.Val248Ile (c.742G>A) is classified Uncertain significance in DCST2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely benign (0.0889); Ultra-rare (popmax 0.0379%, amr).

How common is DCST2 p.Val248Ile (c.742G>A) in the general population?

DCST2 p.Val248Ile (c.742G>A) is ultra-rare (popmax 0.0379%, amr) (gnomAD).

What do computational predictors say about DCST2 p.Val248Ile (c.742G>A)?

AlphaMissense predicts likely benign (score 0.0889) — an in-silico prediction, not a clinical call.

DCST2 p.Val248Ile

c.742G>A · rs550110036 · VCV3080618

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0889 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0379%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0889	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -7.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.4	GERP 0.3, phastCons 0.9
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.075 · regional, not allelic
Overall
CADD	15.92	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 0.0379% Admixed American · 20/52,728 alleles

Filtering AF 0.0251% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0209%

Overall 0.00665% 105/1,577,990 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0379%	2,636
European (non-Finnish)	0.00697%	14,340
Remaining individualsnot grpmax-eligible	0.00656%	15,244

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.Val248Ile
Coding: c.742G>A
MANE Select: NM_144622
dbSNP: rs550110036
Type: single nucleotide variant
Location: chr1:155031232 (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

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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-val248ile (accessed [today's date]).

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