Is ADIG p.Pro24Ser (c.70C>T) pathogenic?

ADIG p.Pro24Ser (c.70C>T) is classified Uncertain significance in ADIG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: ambiguous (0.5336); Ultra-rare (popmax 0.0533%, afr).

How common is ADIG p.Pro24Ser (c.70C>T) in the general population?

ADIG p.Pro24Ser (c.70C>T) is ultra-rare (popmax 0.0533%, afr) (gnomAD).

What do computational predictors say about ADIG p.Pro24Ser (c.70C>T)?

AlphaMissense predicts ambiguous (score 0.5336) — an in-silico prediction, not a clinical call.

ADIG p.Pro24Ser

c.70C>T · rs376564463 · VCV3089399

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5336 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0533%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5336	ambiguous · top 8% in ADIG
REVEL	0.19	benign-leaning
SaProt	LLR -8.01	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 5.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 4,893 bp · p 0.033 · regional, not allelic
Overall
CADD	24.1	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 0.0533% African / African-American · 40/75,042 alleles

Filtering AF 0.0401% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0356%

Overall 0.0026% 42/1,613,986 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0533%	1,876
Middle Eastern	0.0165%	6,046
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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: ADIG
Protein: p.Pro24Ser
Coding: c.70C>T
MANE Select: NM_001393816
dbSNP: rs376564463
Type: single nucleotide variant
Location: chr20:38581320 (GRCh38)
Gene constraint: LOEUF 1.845 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.94

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

Similar variants

ADIG c.20C>A Uncertain significance ★ same type
ADIG p.Arg36His Uncertain significance ★ ⚠ same type
ADIG p.Arg77Lys Uncertain significance ★ ⚠ same type
ADIG p.Leu38Phe Uncertain significance ★ ⚠ same type
ADIG p.Leu39Phe Uncertain significance ★ ⚠ same type
ADIG p.Phe64Val Uncertain significance ★ ⚠ same type
ADIG p.Pro7Leu Uncertain significance ★ ⚠ same type
ADIG p.Ser49Arg 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/adig-p-pro24ser (accessed [today's date]).

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