Is IFT57 p.Arg71Ter (c.211A>T) pathogenic?

IFT57 p.Arg71Ter (c.211A>T) is classified Uncertain significance in IFT57 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-07-06). Very rare (popmax 0.000341%, nfe); Associated with Fetal anomalies with a likely genetic cause.

What condition is associated with IFT57 p.Arg71Ter (c.211A>T)?

IFT57 p.Arg71Ter (c.211A>T) is associated with Fetal anomalies with a likely genetic cause (ClinVar).

How common is IFT57 p.Arg71Ter (c.211A>T) in the general population?

IFT57 p.Arg71Ter (c.211A>T) is very rare (popmax 0.000341%, nfe) (gnomAD).

IFT57 p.Arg71Ter

c.211A>T · VCV4887979

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000341%, nfe)

Conditions

Fetal anomalies with a likely genetic cause

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 11
REVEL	0.289	benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Overall
CADD	45.0	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 0.000341% European (non-Finnish) · 4/1,172,472 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000501% 8/1,597,988 alleles · very rare exomes 7/1,445,834 · genomes 1/152,154 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0064%	15,627
European (non-Finnish)grpmax	0.000341%	293,118

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: IFT57
Protein: p.Arg71Ter
Coding: c.211A>T
MANE Select: NM_018010
Type: single nucleotide variant
Location: chr3:108222112 (GRCh38)
Gene constraint: LOEUF 1.425 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.92

Full IFT57 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Fetal anomalies with a likely genetic cause

Similar variants

IFT57 c.585+3A>G Likely pathogenic ★★ same type
IFT57 c.981+4A>G Uncertain significance ★★ same type
IFT57 p.Ala155Thr Uncertain significance ★★ ⚠ same type
IFT57 p.Ala37Val Uncertain significance ★★ ⚠ same type
IFT57 p.Arg245Cys Uncertain significance ★★ ⚠ same type
IFT57 p.Asp110Ala Uncertain significance ★★ ⚠ same type
IFT57 p.Asp219His Uncertain significance ★★ ⚠ same type
IFT57 p.Asp228His 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/ift57-p-arg71ter (accessed [today's date]).

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