Is CALD1 p.Ser171Phe (c.512C>T) pathogenic?

CALD1 p.Ser171Phe (c.512C>T) is classified Benign in CALD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1967); Common (popmax 5.08%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CALD1 p.Ser171Phe (c.512C>T)?

AlphaMissense predicts likely benign (score 0.1967) — an in-silico prediction, not a clinical call.

CALD1 p.Ser171Phe

Q: How common is CALD1 p.Ser171Phe (c.512C>T) in the general population?

CALD1 p.Ser171Phe (c.512C>T) is common (popmax 5.08%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.512C>T · rs114442219 · VCV773905

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1967 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.08%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1967	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -9.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 608 bp · p 0.95 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.08% African / African-American · 3,572/70,264 alleles

Filtering AF 4.94% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.89%

Overall 0.263% 4,191/1,595,466 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.08%	20
Middle Eastern	0.364%	275
Remaining individualsnot grpmax-eligible	0.325%	307
Admixed American	0.314%	319
European (non-Finnish)	0.0169%	5,929
South Asian	0.0146%	6,854
Ashkenazi Jewishnot grpmax-eligible	0.0102%	9,797

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: CALD1
Protein: p.Ser171Phe
Coding: c.512C>T
MANE Select: NM_033138
dbSNP: rs114442219
Type: single nucleotide variant
Location: chr7:134933281 (GRCh38)
Gene constraint: LOEUF 0.498 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 65.68
Residue 171: the 'myosin and calmodulin-binding' region; the 'disordered' region

Full CALD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CALD1 p.Ala324Glu Benign ★★ ⚠ same type
CALD1 p.Asp122Asn Likely benign ★★ ⚠ same type
CALD1 p.Glu77Lys Benign ★★ ⚠ same type
CALD1 p.Ile671Val Benign ★★ same type
CALD1 p.Met257Ile Likely benign ★★ same type
CALD1 p.Ala265Thr Uncertain significance ★ ⚠ same type
CALD1 p.Ala282Val Uncertain significance ★ ⚠ same type
CALD1 p.Ala303Ser 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/cald1-p-ser171phe (accessed [today's date]).

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