Is KCNQ3 p.Ala26Val (c.77C>T) pathogenic?

KCNQ3 p.Ala26Val (c.77C>T) is classified Likely benign in KCNQ3 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-12-04). AlphaMissense: likely benign (0.1823); Very rare (popmax 0.00297%, sas); Associated with Inborn genetic diseases.

What condition is associated with KCNQ3 p.Ala26Val (c.77C>T)?

KCNQ3 p.Ala26Val (c.77C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KCNQ3 p.Ala26Val (c.77C>T) in the general population?

KCNQ3 p.Ala26Val (c.77C>T) is very rare (popmax 0.00297%, sas) (gnomAD).

What do computational predictors say about KCNQ3 p.Ala26Val (c.77C>T)?

AlphaMissense predicts likely benign (score 0.1823) — an in-silico prediction, not a clinical call.

KCNQ3 p.Ala26Val

c.77C>T · rs2130875326 · VCV1760679

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1823 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00297%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1823	likely benign
REVEL	0.337	indeterminate
SaProt	LLR -7.92	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.8	GERP -1.1, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 337 bp · p 0.24 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00297% South Asian · 1/33,702 alleles

Overall 7.8e-05% 1/1,282,696 alleles · very rare exomes 1/1,133,338 · genomes 0/149,358 · joint denominator

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: KCNQ3
Protein: p.Ala26Val
Coding: c.77C>T
MANE Select: NM_004519
dbSNP: rs2130875326
Type: single nucleotide variant
Location: chr8:132480456 (GRCh38)
Gene constraint: LOEUF 0.458 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 57.50 · 35 PDB
Residue 26: the 'disordered' region

Full KCNQ3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KCNQ3 c.387-3T>C Uncertain significance ★★ same condition
KCNQ3 p.Ala177Asp Uncertain significance ★★ ⚠ same condition
KCNQ3 p.Ala25Thr Uncertain significance ★★ ⚠ same condition
KCNQ3 p.Ala334Thr Uncertain significance ★★ ⚠ same condition
KCNQ3 p.Ala497Glu Uncertain significance ★★ ⚠ same condition
KCNQ3 p.Ala714Val Uncertain significance ★★ ⚠ same condition
KCNQ3 p.Arg431His Uncertain significance ★★ ⚠ same condition
KCNQ3 p.Arg649Gln Uncertain significance ★★ ⚠ 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/kcnq3-p-ala26val (accessed [today's date]).

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