Is HTT p.Phe2717Tyr (c.8150T>A) pathogenic?

HTT p.Phe2717Tyr (c.8150T>A) is classified Pathogenic in HTT (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-09-09). AlphaMissense: likely benign (0.1897); Absent from gnomAD v4.1; Associated with Lopes-Maciel-Rodan syndrome.

What condition is associated with HTT p.Phe2717Tyr (c.8150T>A)?

HTT p.Phe2717Tyr (c.8150T>A) is associated with Lopes-Maciel-Rodan syndrome (ClinVar).

How common is HTT p.Phe2717Tyr (c.8150T>A) in the general population?

HTT p.Phe2717Tyr (c.8150T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HTT p.Phe2717Tyr (c.8150T>A)?

AlphaMissense predicts likely benign (score 0.1897) — an in-silico prediction, not a clinical call.

HTT p.Phe2717Tyr

c.8150T>A · rs1060505028 · VCV417745

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1897 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Lopes-Maciel-Rodan syndrome

Computational evidence

Protein change
AlphaMissense	0.1897	likely benign ⚠ discordant with ClinVar
REVEL	0.166	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: HTT
Protein: p.Phe2717Tyr
Coding: c.8150T>A
MANE Select: NM_001045 · reported on NM_001388492
dbSNP: rs1060505028
Type: single nucleotide variant
Location: chr4:3229927 (GRCh38)
Structure: AlphaFold pLDDT 85.38 · 30 PDB

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

Disease context

Lopes-Maciel-Rodan syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

HTT p.Phe2717Leu Uncertain significance ★ ⚠ same residue
HTT p.Asp920Asn Uncertain significance ★★ same condition
HTT p.Gly2968Asp Uncertain significance ★★ same condition
HTT p.Leu1237Ile Uncertain significance ★★ ⚠ same condition
HTT p.Pro703Leu Uncertain significance ★★ ⚠ same condition
HTT c.7765+10G>A Benign/Likely benign ★★ same condition
HTT p.Thr1260Met Benign ★★ same condition
HTT p.Val1546= Benign/Likely benign ★★ same condition

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/htt-p-phe2717tyr (accessed [today's date]).

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