Is TTC7A p.Ser15Phe (c.44C>T) pathogenic?

TTC7A p.Ser15Phe (c.44C>T) is classified Conflicting classifications of pathogenicity in TTC7A (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-11-25). Rare (popmax 0.651%, sas).

How common is TTC7A p.Ser15Phe (c.44C>T) in the general population?

TTC7A p.Ser15Phe (c.44C>T) is rare (popmax 0.651%, sas) (gnomAD).

TTC7A p.Ser15Phe

c.44C>T · rs555979766 · VCV2498818

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.651%, sas)

⚠ 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.
REVEL	0.028	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.7	GERP 0.19
Overall
CADD	10.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.651% South Asian · 438/67,250 alleles

Filtering AF 0.601% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.581%

Overall 0.0778% 545/700,616 alleles · rare exomes 506/548,522 · genomes 39/152,094 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.651%	154
Remaining individualsnot grpmax-eligible	0.0521%	1,919
Middle Eastern	0.0459%	2,179
European (non-Finnish)	0.0211%	4,746
Admixed American	0.00807%	12,388
Finnishnot grpmax-eligible	0.00456%	21,948
African / African-American	0.00175%	57,102

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: TTC7A
Protein: p.Ser15Phe
Coding: c.44C>T
MANE Select: NM_020458 · reported on NM_001288953
dbSNP: rs555979766
Type: single nucleotide variant
Location: chr2:46917239 (GRCh38)

Full TTC7A 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/ttc7a-p-ser15phe (accessed [today's date]).

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