Is ADPRM p.Ser86Pro (c.256T>C) pathogenic?

ADPRM p.Ser86Pro (c.256T>C) is classified Uncertain significance in ADPRM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-03). AlphaMissense: ambiguous (0.5255); Very rare (popmax 0.00267%, afr).

How common is ADPRM p.Ser86Pro (c.256T>C) in the general population?

ADPRM p.Ser86Pro (c.256T>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ADPRM p.Ser86Pro (c.256T>C)?

AlphaMissense predicts ambiguous (score 0.5255) — an in-silico prediction, not a clinical call.

ADPRM p.Ser86Pro

c.256T>C · rs765697723 · VCV2269628

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5255 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5255	ambiguous
REVEL	0.702	pathogenic-leaning
SaProt	LLR -12.66	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 6,214 bp · p 0.00019 · regional, not allelic
Overall
CADD	22.3	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 0.00267% African / African-American · 2/75,018 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000821% 12/1,461,862 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,509
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)	0.000763%	131,111

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: ADPRM
Protein: p.Ser86Pro
Coding: c.256T>C
MANE Select: NM_020233
dbSNP: rs765697723
Type: single nucleotide variant
Location: chr17:10705182 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.59

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

Similar variants

ADPRM p.Ala248Thr Uncertain significance ★ ⚠ same type
ADPRM p.Ala24Val Uncertain significance ★ ⚠ same type
ADPRM p.Arg16Cys Uncertain significance ★ ⚠ same type
ADPRM p.Arg324Lys Uncertain significance ★ ⚠ same type
ADPRM p.Arg42Trp Uncertain significance ★ ⚠ same type
ADPRM p.Asn80Lys Uncertain significance ★ ⚠ same type
ADPRM p.Asp74Glu Uncertain significance ★ ⚠ same type
ADPRM p.Asp77Asn 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/adprm-p-ser86pro (accessed [today's date]).

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