Is ARID4A p.Val38Ile (c.112G>A) pathogenic?

ARID4A p.Val38Ile (c.112G>A) is classified Uncertain significance in ARID4A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-19). AlphaMissense: ambiguous (0.4371); Ultra-rare (popmax 0.0165%, mid).

How common is ARID4A p.Val38Ile (c.112G>A) in the general population?

ARID4A p.Val38Ile (c.112G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ARID4A p.Val38Ile (c.112G>A)?

AlphaMissense predicts ambiguous (score 0.4371) — an in-silico prediction, not a clinical call.

ARID4A p.Val38Ile

c.112G>A · rs148954262 · VCV3129453

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4371 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4371	ambiguous
REVEL	0.142	moderately benign-leaning
SaProt	LLR -7.07	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 4,397 bp · p 0.19 · regional, not allelic
Overall
CADD	25.7	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 0.0165% Middle Eastern · 1/6,076 alleles

Filtering AF 0.00827% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00775%

Overall 0.0109% 175/1,611,588 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.152%	657
Middle Easterngrpmax	0.0165%	6,076
Remaining individualsnot grpmax-eligible	0.016%	6,239
European (non-Finnish)	0.00976%	10,245
Admixed American	0.00501%	19,979
South Asian	0.0011%	90,874

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ARID4A
Protein: p.Val38Ile
Coding: c.112G>A
MANE Select: NM_002892
dbSNP: rs148954262
Type: single nucleotide variant
Location: chr14:58301685 (GRCh38)
Gene constraint: LOEUF 0.339 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.77 · 7 PDB
Residue 38: the 'dna-binding' region; a β-strand

Full ARID4A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RBP1 c.438+20T>C Benign ★★ same type
RBP1 p.Met112Val Benign ★★ ⚠ same type
ARID4A c.3211+1G>A Conflicting classifications of pathogenicity ★ same type
ARID4A p.Ala1033Ser Uncertain significance ★ ⚠ same type
ARID4A p.Ala1046Ser Uncertain significance ★ ⚠ same type
ARID4A p.Ala1054Ser Uncertain significance ★ ⚠ same type
ARID4A p.Ala1084Ser Uncertain significance ★ ⚠ same type
ARID4A p.Ala1096Val 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/arid4a-p-val38ile (accessed [today's date]).

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