Is HTT p.Val950Leu (c.2848G>T) pathogenic?

HTT p.Val950Leu (c.2848G>T) is classified Uncertain significance in HTT (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-23). AlphaMissense: likely pathogenic (0.6615); Very rare (popmax 0.00534%, afr).

How common is HTT p.Val950Leu (c.2848G>T) in the general population?

HTT p.Val950Leu (c.2848G>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about HTT p.Val950Leu (c.2848G>T)?

AlphaMissense predicts likely pathogenic (score 0.6615) — an in-silico prediction, not a clinical call.

HTT p.Val950Leu

c.2848G>T · rs372725851 · VCV1363247

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6615 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Computational evidence

Protein change
AlphaMissense	0.6615	likely pathogenic
REVEL	0.33	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	27.1	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 0.00534% African / African-American · 4/74,934 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00173% 28/1,613,990 alleles · very rare exomes 25/1,461,788 · genomes 3/152,202 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,734
European (non-Finnish)	0.00203%	49,165

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.Val950Leu
Coding: c.2848G>T
MANE Select: NM_001388492
dbSNP: rs372725851
Type: single nucleotide variant
Location: chr4:3140559 (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-val950leu (accessed [today's date]).

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