Is ACP6 p.Arg168Trp (c.502C>T) pathogenic?

ACP6 p.Arg168Trp (c.502C>T) is classified Uncertain significance in ACP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-16). AlphaMissense: ambiguous (0.4181); Very rare (popmax 0.00552%, sas).

How common is ACP6 p.Arg168Trp (c.502C>T) in the general population?

ACP6 p.Arg168Trp (c.502C>T) is very rare (popmax 0.00552%, sas) (gnomAD).

What do computational predictors say about ACP6 p.Arg168Trp (c.502C>T)?

AlphaMissense predicts ambiguous (score 0.4181) — an in-silico prediction, not a clinical call.

ACP6 p.Arg168Trp

c.502C>T · rs978886014 · VCV2245658

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4181 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00552%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4181	ambiguous
REVEL	0.858	moderately pathogenic-leaning
SaProt	LLR -13.45	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.47 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 23 kb · p 0.055 · regional, not allelic
Overall
CADD	34.0	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 0.00552% South Asian · 5/90,504 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.0018% 29/1,610,730 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00552%	18,101
European (non-Finnish)	0.00187%	53,579
Admixed American	0.00169%	59,282
Remaining individualsnot grpmax-eligible	0.00161%	62,300

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: ACP6
Protein: p.Arg168Trp
Coding: c.502C>T
MANE Select: NM_016361
dbSNP: rs978886014
Type: single nucleotide variant
Location: chr1:147659017 (GRCh38)
Gene constraint: LOEUF 1.313 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.22 · 3 PDB
Residue 168: the 'substrate binding' region; an α-helix

Full ACP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACP6 p.Arg168Gln Uncertain significance ★ ⚠ same residue
ACP6 p.Arg218Trp Benign ★★ ⚠ same type
ACP6 p.Leu224= Benign ★★ same type
ACP6 p.Val127Met Likely pathogenic ★ ⚠ same type
ACP6 p.Ala196Glu Uncertain significance ★ ⚠ same type
ACP6 p.Ala257Thr Uncertain significance ★ ⚠ same type
ACP6 p.Ala356Thr Uncertain significance ★ ⚠ same type
ACP6 p.Ala61Gly 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/acp6-p-arg168trp (accessed [today's date]).

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