Is ATP23 p.Ala229Val (c.686C>T) pathogenic?

ATP23 p.Ala229Val (c.686C>T) is classified Likely benign in ATP23 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-01). AlphaMissense: ambiguous (0.3628); Low-frequency (popmax 1.11%, mid).

How common is ATP23 p.Ala229Val (c.686C>T) in the general population?

ATP23 p.Ala229Val (c.686C>T) is low-frequency (popmax 1.11%, mid) (gnomAD).

What do computational predictors say about ATP23 p.Ala229Val (c.686C>T)?

AlphaMissense predicts ambiguous (score 0.3628) — an in-silico prediction, not a clinical call.

ATP23 p.Ala229Val

c.686C>T · rs117230607 · VCV2643153

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3628 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.11%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3628	ambiguous
REVEL	0.121	moderately benign-leaning
SaProt	LLR -12.69	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.35	donor gain · deltas
Pangolin	Δ0.69	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.4	GERP 1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 15 kb · p 0.064 · regional, not allelic
Overall
CADD	25.1	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 1.11% Middle Eastern · 67/6,058 alleles

Filtering AF 0.893% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.816%

Overall 0.623% 10,049/1,613,702 alleles · low-frequency

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.24%	80
Middle Easterngrpmax	1.11%	90
Admixed American	0.725%	138
Remaining individualsnot grpmax-eligible	0.717%	139
European (non-Finnish)	0.712%	140
South Asian	0.171%	584
Finnishnot grpmax-eligible	0.145%	688
African / African-American	0.105%	949
East Asian	0.00223%	44,806

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ATP23
Protein: p.Ala229Val
Coding: c.686C>T
MANE Select: NM_033276
dbSNP: rs117230607
Type: single nucleotide variant
Location: chr12:57956835 (GRCh38)
Gene constraint: LOEUF 1.16 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.25

Full ATP23 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATP23 p.Gln38= Likely benign ★ 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/atp23-p-ala229val (accessed [today's date]).

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