Is DISP1 p.Ser347Phe (c.1040C>T) pathogenic?

DISP1 p.Ser347Phe (c.1040C>T) is classified Uncertain significance in DISP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.2666); Very rare (popmax 0.00167%, amr).

How common is DISP1 p.Ser347Phe (c.1040C>T) in the general population?

DISP1 p.Ser347Phe (c.1040C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DISP1 p.Ser347Phe (c.1040C>T)?

AlphaMissense predicts likely benign (score 0.2666) — an in-silico prediction, not a clinical call.

DISP1 p.Ser347Phe

c.1040C>T · VCV4660220

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2666 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2666	likely benign
REVEL	0.759	pathogenic-leaning
SaProt	LLR -8.80	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 63 kb · p 8.4e-11 · regional, not allelic
Overall
CADD	27.4	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 0.00167% Admixed American · 1/60,022 alleles

Overall 6.84e-05% 1/1,461,892 alleles · very rare

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: DISP1
Protein: p.Ser347Phe
Coding: c.1040C>T
MANE Select: NM_001377229
Type: single nucleotide variant
Location: chr1:223002437 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 65.21 · 4 PDB
Residue 347: a UniProt-annotated variant site (in hpe10; uncertain significance; heterozygous variant inherited from unaffected parent)

Full DISP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DISP1 p.Ser347= Likely benign ★ same residue
DISP1 p.Ala1123Thr Uncertain significance ★★ ⚠ same type
DISP1 p.Ala1204Thr Uncertain significance ★★ ⚠ same type
DISP1 p.Ala248Val Uncertain significance ★★ ⚠ same type
DISP1 p.Ala733Val Uncertain significance ★★ ⚠ same type
DISP1 p.Arg1061His Uncertain significance ★★ ⚠ same type
DISP1 p.Arg718His Uncertain significance ★★ ⚠ same type
DISP1 p.Arg763His 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/disp1-p-ser347phe (accessed [today's date]).

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