Is AJAP1 p.Ala35Val (c.104C>T) pathogenic?

AJAP1 p.Ala35Val (c.104C>T) is classified Benign in AJAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-02-25). AlphaMissense: likely benign (0.1326); Low-frequency (popmax 1.44%, afr).

How common is AJAP1 p.Ala35Val (c.104C>T) in the general population?

AJAP1 p.Ala35Val (c.104C>T) is low-frequency (popmax 1.44%, afr) (gnomAD).

What do computational predictors say about AJAP1 p.Ala35Val (c.104C>T)?

AlphaMissense predicts likely benign (score 0.1326) — an in-silico prediction, not a clinical call.

AJAP1 p.Ala35Val

c.104C>T · rs149284997 · VCV787731

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1326 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.44%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1326	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -5.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.93	GERP 0.39, phastCons 0.42
Regional constraint	o/e 1.03	unconstrained · MANE · 119 kb · p 0.53 · regional, not allelic
Overall
CADD	20.8	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 1.44% African / African-American · 1,041/72,058 alleles

Filtering AF 1.37% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.34%

Overall 0.109% 1,737/1,588,056 alleles · low-frequency exomes 1,096/1,435,792 · genomes 641/152,264 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.44%	69
Middle Eastern	0.617%	162
Remaining individualsnot grpmax-eligible	0.249%	402
Admixed American	0.153%	654
Ashkenazi Jewishnot grpmax-eligible	0.0978%	1,022
South Asian	0.0458%	2,184
European (non-Finnish)	0.03%	3,329
East Asian	0.00238%	42,000

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: AJAP1
Protein: p.Ala35Val
Coding: c.104C>T
MANE Select: NM_018836
dbSNP: rs149284997
Type: single nucleotide variant
Location: chr1:4711974 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.22

Full AJAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AJAP1 p.Pro228Arg Uncertain significance ★★ ⚠ same type
AJAP1 p.Ser260Gly Uncertain significance ★★ ⚠ same type
AJAP1 p.Gly202Asp Benign ★★ same type
AJAP1 p.Ala115Thr Uncertain significance ★ ⚠ same type
AJAP1 p.Ala122Thr Uncertain significance ★ ⚠ same type
AJAP1 p.Ala123Thr Uncertain significance ★ ⚠ same type
AJAP1 p.Ala142Val Uncertain significance ★ ⚠ same type
AJAP1 p.Ala150Thr 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/ajap1-p-ala35val (accessed [today's date]).

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