Is DISP2 p.Thr470Ser (c.1408A>T) pathogenic?

DISP2 p.Thr470Ser (c.1408A>T) is classified Uncertain significance in DISP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.1653); Rare (popmax 0.326%, afr).

How common is DISP2 p.Thr470Ser (c.1408A>T) in the general population?

DISP2 p.Thr470Ser (c.1408A>T) is rare (popmax 0.326%, afr) (gnomAD).

What do computational predictors say about DISP2 p.Thr470Ser (c.1408A>T)?

AlphaMissense predicts likely benign (score 0.1653) — an in-silico prediction, not a clinical call.

DISP2 p.Thr470Ser

c.1408A>T · VCV4660236

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1653 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.326%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1653	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -5.92	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 7.1	GERP 1.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 2,889 bp · p 0.52 · regional, not allelic
Overall
CADD	18.07	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 0.326% African / African-American · 244/74,858 alleles

Filtering AF 0.292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.279%

Overall 0.016% 258/1,613,554 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.326%	307
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Admixed American	0.00834%	11,997
European (non-Finnish)	8.48e-05%	1,179,938

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: DISP2
Protein: p.Thr470Ser
Coding: c.1408A>T
MANE Select: NM_033510
Type: single nucleotide variant
Location: chr15:40367520 (GRCh38)
Gene constraint: LOEUF 0.813 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.24

Full DISP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DISP2 p.Pro194= Benign ★★ same type
DISP2 p.Ala1053Thr Uncertain significance ★ ⚠ same type
DISP2 p.Ala1069Gly Uncertain significance ★ ⚠ same type
DISP2 p.Ala1128Ser Uncertain significance ★ ⚠ same type
DISP2 p.Ala1128Val Uncertain significance ★ ⚠ same type
DISP2 p.Ala1210Gly Uncertain significance ★ ⚠ same type
DISP2 p.Ala1343Pro Uncertain significance ★ ⚠ same type
DISP2 p.Ala1343Val 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/disp2-p-thr470ser (accessed [today's date]).

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