Is APMAP p.Asp243His (c.727G>C) pathogenic?

APMAP p.Asp243His (c.727G>C) is classified Uncertain significance in APMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-23). AlphaMissense: ambiguous (0.4279); Very rare (popmax 0.00167%, amr).

How common is APMAP p.Asp243His (c.727G>C) in the general population?

APMAP p.Asp243His (c.727G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about APMAP p.Asp243His (c.727G>C)?

AlphaMissense predicts ambiguous (score 0.4279) — an in-silico prediction, not a clinical call.

APMAP p.Asp243His

c.727G>C · rs773138592 · VCV2246574

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4279 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
AlphaMissense	0.4279	ambiguous
REVEL	0.328	indeterminate
SaProt	LLR -14.14	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 29 kb · p 0.066 · regional, not allelic
Overall
CADD	23.2	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 0.00167% Admixed American · 1/59,990 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000958% 14/1,460,772 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,990
European (non-Finnish)	0.0011%	90,706

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: APMAP
Protein: p.Asp243His
Coding: c.727G>C
MANE Select: NM_020531
dbSNP: rs773138592
Type: single nucleotide variant
Location: chr20:24969647 (GRCh38)
Gene constraint: LOEUF 1.14 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.60

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

Similar variants

APMAP p.Ala47Gly Uncertain significance ★ ⚠ same type
APMAP p.Arg120Trp Uncertain significance ★ ⚠ same type
APMAP p.Arg134Gln Uncertain significance ★ ⚠ same type
APMAP p.Arg134Pro Uncertain significance ★ ⚠ same type
APMAP p.Arg143Gly Uncertain significance ★ ⚠ same type
APMAP p.Arg156Cys Uncertain significance ★ ⚠ same type
APMAP p.Arg156His Uncertain significance ★ ⚠ same type
APMAP p.Arg224Gln 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/apmap-p-asp243his (accessed [today's date]).

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