Is HTT p.Phe2717Leu (c.8151T>A) pathogenic?

HTT p.Phe2717Leu (c.8151T>A) is classified Uncertain significance in HTT (ClinVar, Single submitter, 1 submitter; last evaluated 2016-04-18). AlphaMissense: likely pathogenic (0.9955); Absent from gnomAD v4.1.

How common is HTT p.Phe2717Leu (c.8151T>A) in the general population?

HTT p.Phe2717Leu (c.8151T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HTT p.Phe2717Leu (c.8151T>A)?

AlphaMissense predicts likely pathogenic (score 0.9955) — an in-silico prediction, not a clinical call.

HTT p.Phe2717Leu

c.8151T>A · rs1085307052 · VCV225542

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9955 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.9955	likely pathogenic · top 1% in HTT
REVEL	0.225	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.51	GERP -3, phastCons 0.11
Overall
CADD	20.3	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.Phe2717Leu
Coding: c.8151T>A
MANE Select: NM_001388492
dbSNP: rs1085307052
Type: single nucleotide variant
Location: chr4:3229928 (GRCh38)
Structure: AlphaFold pLDDT 85.38 · 30 PDB

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

Similar variants

HTT p.Phe2717Tyr Pathogenic ⚠ same residue
HTT c.889+6G>T Uncertain significance ★★ same type
HTT p.Ala2739Thr Uncertain significance ★★ same type
HTT p.Arg1654Trp Uncertain significance ★★ same type
HTT p.Arg1945Trp Uncertain significance ★★ same type
HTT p.Asp1157Gly Uncertain significance ★★ same type
HTT p.Asp920Asn Uncertain significance ★★ same type
HTT p.Glu449Ala 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/htt-p-phe2717leu (accessed [today's date]).

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