Is IFRD1 p.Ser95= (c.285T>C) pathogenic?

IFRD1 p.Ser95= (c.285T>C) is classified Likely benign in IFRD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). Very rare (popmax 0.00669%, eas).

How common is IFRD1 p.Ser95= (c.285T>C) in the general population?

IFRD1 p.Ser95= (c.285T>C) is very rare (popmax 0.00669%, eas) (gnomAD).

IFRD1 p.Ser95=

c.285T>C · rs756796129 · VCV3108331

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.019	GERP 0.56, phastCons 0.92
Overall
CADD	12.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,854 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000186% 3/1,613,694 alleles · very rare exomes 3/1,461,390 · genomes 0/152,304 · joint denominator

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: IFRD1
Protein: p.Ser95=
Coding: c.285T>C
MANE Select: NM_001550
dbSNP: rs756796129
Type: single nucleotide variant
Location: chr7:112456914 (GRCh38)
Gene constraint: LOEUF 0.815 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.46

Full IFRD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IFRD1 c.619-5A>G Benign ★★ same type
IFRD1 p.Leu212Val Benign ★★ same type
IFRD1 p.Leu71= Benign ★★ same type
IFRD1 p.Ala101Glu Uncertain significance ★ ⚠ same type
IFRD1 p.Ala25Thr Uncertain significance ★ ⚠ same type
IFRD1 p.Ala31Thr Uncertain significance ★ ⚠ same type
IFRD1 p.Ala445Thr Uncertain significance ★ ⚠ same type
IFRD1 p.Ala46Thr 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/ifrd1-p-ser95 (accessed [today's date]).

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