Is HTT p.Ala805Val (c.2414C>T) pathogenic?

HTT p.Ala805Val (c.2414C>T) is classified Conflicting classifications of pathogenicity in HTT (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-02). AlphaMissense: likely benign (0.0693); Ultra-rare (popmax 0.0267%, eas).

How common is HTT p.Ala805Val (c.2414C>T) in the general population?

HTT p.Ala805Val (c.2414C>T) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

What do computational predictors say about HTT p.Ala805Val (c.2414C>T)?

AlphaMissense predicts likely benign (score 0.0693) — an in-silico prediction, not a clinical call.

HTT p.Ala805Val

c.2414C>T · VCV3361821

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0693 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0693	likely benign
REVEL	0.284	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8.5	GERP -3.3
Overall
CADD	0.444	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 0.0267% East Asian · 12/44,882 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00211% 34/1,613,890 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,740
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0096%	10,416
South Asian	0.00329%	30,355
African / African-American	0.00267%	37,508
European (non-Finnish)	0.000848%	117,981

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.Ala805Val
Coding: c.2414C>T
MANE Select: NM_001045 · reported on NM_001388492
Type: single nucleotide variant
Location: chr4:3132832 (GRCh38)
Structure: AlphaFold pLDDT 85.38 · 30 PDB

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

Similar variants

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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-ala805val (accessed [today's date]).

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