Is DISP1 p.Phe706= (c.2118C>T) pathogenic?

DISP1 p.Phe706= (c.2118C>T) is classified Likely benign in DISP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-24). Ultra-rare (popmax 0.025%, amr).

How common is DISP1 p.Phe706= (c.2118C>T) in the general population?

DISP1 p.Phe706= (c.2118C>T) is ultra-rare (popmax 0.025%, amr) (gnomAD).

DISP1 p.Phe706=

c.2118C>T · rs201599231 · VCV2888502

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.7	phastCons 0.024
Overall
CADD	5.466	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.025% Admixed American · 15/60,006 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.00502% 81/1,613,976 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.025%	4,000
Remaining individualsnot grpmax-eligible	0.0096%	10,418
European (non-Finnish)	0.00449%	22,264
African / African-American	0.004%	24,999
South Asian	0.00329%	30,359
Finnishnot grpmax-eligible	0.00156%	63,948

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.Phe706=
Coding: c.2118C>T
MANE Select: NM_001377229
dbSNP: rs201599231
Type: single nucleotide variant
Location: chr1:223003515 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 65.21 · 4 PDB
Residue 706: a UniProt-annotated variant site (in hpe10; uncertain significance; heterozygous variant inherited from unaffected parent); a UniProt-annotated variant site (in hpe10; uncertain significance; heterozygous variant inherited from unaffected parent; the orthologous mouse mutation results in severely decreased extracellular release of shh)

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

Similar variants

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
DISP1 p.Asn1035Ser 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-phe706 (accessed [today's date]).

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