Is HTT p.Val1064Ile (c.3190G>A) pathogenic?

HTT p.Val1064Ile (c.3190G>A) is classified Benign in HTT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0818); Common (popmax 6.22%, nfe) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about HTT p.Val1064Ile (c.3190G>A)?

AlphaMissense predicts likely benign (score 0.0818) — an in-silico prediction, not a clinical call.

HTT p.Val1064Ile

Q: How common is HTT p.Val1064Ile (c.3190G>A) in the general population?

HTT p.Val1064Ile (c.3190G>A) is common (popmax 6.22%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3190G>A · rs35892913 · VCV1569339

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0818 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.22%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0818	likely benign
REVEL	0.064	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 6.5	GERP -0.36, phastCons 1
Overall
CADD	16.4	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

Grpmax group 6.22% European (non-Finnish) · 73,355/1,179,792 alleles

Filtering AF 6.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.16%

Overall 5.31% 85,702/1,613,910 alleles · common exomes 79,437/1,461,626 · genomes 6,265/152,284 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	6.22%	16
Middle Eastern	5.13%	19
Remaining individualsnot grpmax-eligible	5.03%	20
Amishnot grpmax-eligible	4.39%	23
Admixed American	4.32%	23
Finnishnot grpmax-eligible	4.13%	24
Ashkenazi Jewishnot grpmax-eligible	3.19%	31
South Asian	2.01%	50
African / African-American	1.12%	90
East Asian	0.0178%	5,611

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: HTT
Protein: p.Val1064Ile
Coding: c.3190G>A
MANE Select: NM_001388492
dbSNP: rs35892913
Type: single nucleotide variant
Location: chr4:3146843 (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 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
HTT p.Gly2084Arg 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-val1064ile (accessed [today's date]).

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