Is IGF2 p.Ser95= (c.285G>A) pathogenic?

IGF2 p.Ser95= (c.285G>A) is classified Likely benign in IGF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). Ultra-rare (popmax 0.0165%, mid).

How common is IGF2 p.Ser95= (c.285G>A) in the general population?

IGF2 p.Ser95= (c.285G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

IGF2 p.Ser95=

c.285G>A · rs554586231 · VCV1897408

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.4	GERP -3
Overall
CADD	9.248	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,054 alleles

Filtering AF 0.00774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00298% 48/1,612,452 alleles · ultra-rare exomes 42/1,460,186 · genomes 6/152,266 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,054
Admixed American	0.015%	6,661
Remaining individualsnot grpmax-eligible	0.0048%	20,822
European (non-Finnish)	0.00288%	34,696
Finnishnot grpmax-eligible	0.00159%	63,076

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: IGF2
Protein: p.Ser95=
Coding: c.285G>A
MANE Select: NM_000612
dbSNP: rs554586231
Type: single nucleotide variant
Location: chr11:2133538 (GRCh38)

Full IGF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/igf2-p-ser95 (accessed [today's date]).

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