Is APMAP p.Arg238Cys (c.712C>T) pathogenic?

APMAP p.Arg238Cys (c.712C>T) is classified Uncertain significance in APMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: ambiguous (0.5176); Ultra-rare (popmax 0.0196%, nfe).

How common is APMAP p.Arg238Cys (c.712C>T) in the general population?

APMAP p.Arg238Cys (c.712C>T) is ultra-rare (popmax 0.0196%, nfe) (gnomAD).

What do computational predictors say about APMAP p.Arg238Cys (c.712C>T)?

AlphaMissense predicts ambiguous (score 0.5176) — an in-silico prediction, not a clinical call.

APMAP p.Arg238Cys

c.712C>T · rs767448339 · VCV3127884

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5176 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0196%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5176	ambiguous
REVEL	0.821	moderately pathogenic-leaning
SaProt	LLR -15.21	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.26	donor gain · deltas
Pangolin	Δ0.32	loss · gain 0.16 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 29 kb · p 0.066 · regional, not allelic
Overall
CADD	35.0	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 0.0196% European (non-Finnish) · 231/1,179,988 alleles

Filtering AF 0.0175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.015% 242/1,613,964 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0196%	5,108
African / African-American	0.00801%	12,486
Remaining individualsnot grpmax-eligible	0.0064%	15,621
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598

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.Arg238Cys
Coding: c.712C>T
MANE Select: NM_020531
dbSNP: rs767448339
Type: single nucleotide variant
Location: chr20:24970198 (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-arg238cys (accessed [today's date]).

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