Is ADD1 p.Val237Ile (c.709G>A) pathogenic?

ADD1 p.Val237Ile (c.709G>A) is classified Likely benign in ADD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.0593); Ultra-rare (popmax 0.0811%, afr).

How common is ADD1 p.Val237Ile (c.709G>A) in the general population?

ADD1 p.Val237Ile (c.709G>A) is ultra-rare (popmax 0.0811%, afr) (gnomAD).

What do computational predictors say about ADD1 p.Val237Ile (c.709G>A)?

AlphaMissense predicts likely benign (score 0.0593) — an in-silico prediction, not a clinical call.

ADD1 p.Val237Ile

c.709G>A · rs140019569 · VCV3082731

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0593 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0811%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0593	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -7.45	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 1	GERP -3.8, phastCons 0.11
Regional constraint	o/e 0.93	unconstrained · MANE · 53 kb · p 0.026 · regional, not allelic
Overall
CADD	1.745	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 0.0811% African / African-American · 60/73,972 alleles

Filtering AF 0.0646% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0587%

Overall 0.00424% 68/1,602,934 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0811%	1,233
Admixed American	0.00177%	56,590
Remaining individualsnot grpmax-eligible	0.00161%	62,052
South Asian	0.00113%	88,324
European (non-Finnish)	0.000425%	235,407

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: ADD1
Protein: p.Val237Ile
Coding: c.709G>A
MANE Select: NM_001354761
dbSNP: rs140019569
Type: single nucleotide variant
Location: chr4:2894699 (GRCh38)
Gene constraint: LOEUF 0.387 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.73

Full ADD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADD1 p.Val234= Benign ★★ same type
ADD1 p.Val559Met Benign ★★ same type
ADD1 c.2047+530G>A Uncertain significance ★ same type
ADD1 c.2047+541G>T Uncertain significance ★ same type
ADD1 p.Ala137Val Uncertain significance ★ ⚠ same type
ADD1 p.Ala151Thr Uncertain significance ★ ⚠ same type
ADD1 p.Ala156Thr Uncertain significance ★ ⚠ same type
ADD1 p.Ala18Thr 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/add1-p-val237ile (accessed [today's date]).

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