Is ADAD1 p.Ser40Phe (c.119C>T) pathogenic?

ADAD1 p.Ser40Phe (c.119C>T) is classified Uncertain significance in ADAD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-02). AlphaMissense: likely benign (0.0932); Very rare (popmax 0.00267%, afr).

How common is ADAD1 p.Ser40Phe (c.119C>T) in the general population?

ADAD1 p.Ser40Phe (c.119C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ADAD1 p.Ser40Phe (c.119C>T)?

AlphaMissense predicts likely benign (score 0.0932) — an in-silico prediction, not a clinical call.

ADAD1 p.Ser40Phe

c.119C>T · rs1794820432 · VCV2519130

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0932 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0932	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -7.90	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 2.1	GERP 0.62, phastCons 0.008
Regional constraint	o/e 0.91	unconstrained · MANE · 50 kb · p 0.013 · regional, not allelic
Overall
CADD	11.79	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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 · 2/74,906 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,614,006 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,453
European (non-Finnish)	8.47e-05%	1,180,027

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: ADAD1
Protein: p.Ser40Phe
Coding: c.119C>T
MANE Select: NM_139243
dbSNP: rs1794820432
Type: single nucleotide variant
Location: chr4:122380188 (GRCh38)
Gene constraint: LOEUF 0.778 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.19

Full ADAD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAD1 p.Ala183Val Uncertain significance ★ ⚠ same type
ADAD1 p.Ala352Thr Uncertain significance ★ ⚠ same type
ADAD1 p.Ala430Thr Uncertain significance ★ ⚠ same type
ADAD1 p.Ala460Thr Uncertain significance ★ ⚠ same type
ADAD1 p.Arg216Ser Uncertain significance ★ ⚠ same type
ADAD1 p.Arg279Lys Uncertain significance ★ ⚠ same type
ADAD1 p.Arg508Trp Uncertain significance ★ ⚠ same type
ADAD1 p.Arg517Gln 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/adad1-p-ser40phe (accessed [today's date]).

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