Is ADPRM p.Phe35Leu (c.105T>A) pathogenic?

ADPRM p.Phe35Leu (c.105T>A) is classified Uncertain significance in ADPRM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-18). AlphaMissense: likely pathogenic (0.6); Ultra-rare (popmax 0.0245%, eas).

How common is ADPRM p.Phe35Leu (c.105T>A) in the general population?

ADPRM p.Phe35Leu (c.105T>A) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

What do computational predictors say about ADPRM p.Phe35Leu (c.105T>A)?

AlphaMissense predicts likely pathogenic (score 0.6) — an in-silico prediction, not a clinical call.

ADPRM p.Phe35Leu

c.105T>A · VCV3273646

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6	likely pathogenic
REVEL	0.21	benign-leaning
SaProt	LLR -7.12	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.48	GERP -0.54, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 6,214 bp · p 0.00019 · regional, not allelic
Overall
CADD	15.57	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 0.0245% East Asian · 11/44,882 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.000752% 11/1,461,866 alleles · ultra-rare

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.Phe35Leu
Coding: c.105T>A
MANE Select: NM_020233
Type: single nucleotide variant
Location: chr17:10705031 (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-phe35leu (accessed [today's date]).

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