Is IFITM5 p.Arg34Ter (c.100C>T) pathogenic?

IFITM5 p.Arg34Ter (c.100C>T) is classified Conflicting classifications of pathogenicity in IFITM5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-10). Very rare (popmax 0.00945%, eas); Associated with osteogenesis imperfecta type 5.

What condition is associated with IFITM5 p.Arg34Ter (c.100C>T)?

IFITM5 p.Arg34Ter (c.100C>T) is associated with osteogenesis imperfecta type 5 (ClinVar).

How common is IFITM5 p.Arg34Ter (c.100C>T) in the general population?

IFITM5 p.Arg34Ter (c.100C>T) is very rare (popmax 0.00945%, eas) (gnomAD).

IFITM5 p.Arg34Ter

c.100C>T · rs531009160 · VCV290777

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00945%, eas)

Conditions

osteogenesis imperfecta type 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 2
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -0.008, phastCons 0.99
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00945% East Asian · 4/42,336 alleles

Filtering AF 0.0032% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00188%

Overall 0.0012% 19/1,577,868 alleles · very rare exomes 16/1,425,618 · genomes 3/152,250 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00945%	10,584
Ashkenazi Jewishnot grpmax-eligible	0.00349%	28,628
African / African-American	0.00272%	36,784
Admixed American	0.00182%	54,916
Finnishnot grpmax-eligible	0.00164%	60,800
Remaining individualsnot grpmax-eligible	0.00164%	61,068
European (non-Finnish)	0.000774%	129,258

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: IFITM5
Protein: p.Arg34Ter
Coding: c.100C>T
MANE Select: NM_001025295
dbSNP: rs531009160
Type: single nucleotide variant
Location: chr11:299391 (GRCh38)
Gene constraint: LOEUF 1.83 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.49

Full IFITM5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

osteogenesis imperfecta type 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IFITM5 p.Arg34Gln Uncertain significance ★ ⚠ same residue
IFITM5 c.-14C>T Pathogenic ★★ same condition
IFITM5 p.Ser40Leu Pathogenic ★★ same condition
IFITM5 p.Ser40Trp Pathogenic/Likely pathogenic ★★ same condition
IFITM5 p.Asn48Ser Uncertain significance ★★ same condition
IFITM5 p.Gly27Ala Benign ★★ same condition
IFITM5 p.Pro31Thr Benign/Likely benign ★★ same condition
IFITM5 p.Ser40= Benign ★★ same condition

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/ifitm5-p-arg34ter (accessed [today's date]).

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